Uracil compounds and use thereof

ABSTRACT

The present invention relates to an uracil compound of the formula [I]:  
                 
 
     wherein W represents oxygen, sulfur, imino or C 1  to C 3  alkylimino; Y represents oxygen, sulfur, imino or C 1  to C 3  alkylimino; R 1  represents C 1  to C 3  alkyl or C 1  to C 3  haloalkyl; R 2  represents C 1  to C 3  alkyl; R 4  represents hydrogen or methyl; R 5  represents C 1  to C 6  alkyl, C 1  to C 6  haloalkyl, or the like; x represents halogen, cyano or nitro; X 2  represents hydrogen or halogen; and each of X 3  and X 4  independently represents hydrogen, halogen, C 1  to C 6  alkyl, or the like. The present compound has an excellent herbicidal activity.

[0001] The present invention relates to uracil compounds and usethereof.

[0002] An object of the present invention is to provide compounds havingexcellent herbicidal activity.

[0003] Recently, a number of herbicides are commercially available andused. However, since there are many kinds of weeds to be controlled andgeneration thereof occurs over a long period of time, a herbicide isrequired having higher herbicidal effect, having wider herbicidalspectrum and causing no problem of phytotoxicity on crops.

[0004] U.S. Pat. No. 4,859,229 discloses that certain kinds ofphenyluracil compounds have herbicidal activity, however, thesephenyluracil compounds do not always have sufficient ability as aherbicide. Also WO 97/01541, and WO 98/41093 disclose that kinds ofsubstituted phenoxyphenyl uracil compounds have herbicidal activity,however, the compounds do not always have sufficient ability as aherbicide.

[0005] The present inventors have intensively investigated to findcompounds having excellent herbicidal activity, and resultantly, foundthat uracil compounds of the following formula [I] have excellentherbicidal activity, leading to completion of the present invention.Namely, the present invention provides uracil compounds [I] of theformula [I] (hereinafter, referred to as present compound):

[0006] wherein, W represents oxygen, sulfur, imino or C₁ to C₃alkylimino, Y represents oxygen, sulfur, imino or C₁ to C₃ alkylimino,R¹ represents C₁ to C₃ alkyl or C₁ to C₃ haloalkyl, R²represents C₁ toC₃ alkyl, R⁴ represents hydrogen or methyl, R⁵ represents hydrogen, C₁to C₆ alkyl, C₁ to C₆ haloalkyl, C₃ to C₆ alkenyl, C₃ to C₆ haloalkenyl,C₃ to C₆ alkynyl, or C₃ to C₆ haloalkynyl, X¹ represents halogen, cyano,or nitro, x² represents hydrogen or halogen, and each of X³ and X⁴independently represents hydrogen, halogen, C₁ to C₆ alkyl, C₁ to C₆haloalkyl, C₃ to C₆ alkenyl, C₃ to C₆ haloalkenyl, C₃ to C₆ alkynyl, C₃to C₆ haloalkynyl, C₁ to C₆ alkoxy C₁ to C₆ alkyl, C₁ to C₆ alkoxy, C₁to C₆ haloalkoxy, C₁ to C₆ alkoxycarbonyl C₁ to C₆ alkoxy or cyano, andherbicides comprising each of these compounds as an effective component.

[0007] Further, the present invention also provides aniline compounds[XXXII] of the formula [XXXII]:

[0008] wherein, W represents oxygen, sulfur, imino or C₁ to C₃alkylimino, R¹⁷ represents oxygen or sulfur, R⁴ represents hydrogen ormethyl, R⁵ represents C₁ to C₆ alkyl, C₁ to C₆ haloalkyl, C₃ to C₆alkenyl, C₃ to C₆ haloalkenyl, C₃ to C₆ alkynyl, C₃ to C₆ haloalkynyl,X¹ represents halogen, cyano, or nitro, X² represents hydrogen orhalogen, and each of X³ and X⁴ independently represents hydrogen,halogen, C₁ to C₆ alkyl, C₁ to C₆ haloalkyl, C₃ to C₆ alkenyl, C₃ to C₆haloalkenyl, C₃ to C₆ alkynyl, C₃ to C₆ haloalkynyl, C₁ to C₆ alkoxy C₁to C₆ alkyl, C₁ to C₆ alkoxy, C₁ to C₆ haloalkoxy, C₁ to C₆alkoxycarbonyl C₁ to C₆ alkoxy or cyano,

[0009] compounds [XXXIV] of the formula [XXXIV]:

[0010] wherein, W represents oxygen, sulfur, imino or C₁ to C₃alkylimino, R¹⁷ represents oxygen or sulfur, R⁴ represents hydrogen ormethyl, R⁵ represents C₁ to C₆ alkyl, C₁ to C₆ haloalkyl, C₃ to C₆alkenyl, C₃ to C₆ haloalkenyl, C₃ to C₆ alkynyl, or C₃ to C₆haloalkynyl, R¹⁸ represents C₁ to C₆ alkyl or phenyl, X¹ representshalogen, cyano, or nitro, X² represents hydrogen or halogen, and each ofX³ and X⁴ independently represents hydrogen, halogen, C₁ to C₆ alkyl, C₁to C₆ haloalkyl, C₃ to C₆ alkenyl, C₃ to C₆ haloalkenyl, C₃ to C₆alkynyl, C₃ to C₆ haloalkinyl, C₁ to C₆ alkoxy C₁ to C₆ alkyl, C₁ to C₆alkoxy group, C₁ to C₆ haloalkoxy, C₁ to C₆ alkoxycarbonyl C₁ to C₆alkoxy or cyano group, and

[0011] compounds [XXXIII] of the formula [XXXIII]:

[0012] wherein, W represents oxygen, sulfur, imino or C₁ to C₃alkylimino, R¹⁷ represents oxygen or sulfur, R⁴ represents hydrogen ormethyl, R⁵ represents C₁ to C₆ alkyl, C₁ to C₆ haloalkyl, C₃ to C₆alkenyl, C₃ to C₆ haloalkenyl, C₃ to C₆ alkynyl, or C₃ to C₆haloalkynyl, X¹ represents halogen, cyano, nitro, X² represents hydrogenor halogen, and each of X³ and X⁴ independently represents hydrogen,halogen, C₁ to C₆ alkyl, C₁ to C₆ haloalkyl, C₃ to C₆ alkenyl, C₃ to C₆haloalkenyl, C₃ to C₆ alkynyl group, C₃ to C₆ haloalkynyl group, C₁ toC₆ alkoxy C₁ to C₆ alkyl, C₁ to C₆ alkoxy, C₁ to C₆ haloalkoxy, C₁ to C₆alkoxycarbonyl C₁ to C₆ alkoxy or cyano,

[0013] which are useful as intermediates for producing the presentcompounds.

[0014] In the present invention, the C₁ to C₃ alkylimino represented byW includes methylimino, ethylimino and the like,

[0015] the C₁ to C₃ alkylimino represented by Y includes methylimino,ethylimino and the like,

[0016] the C₁ to C₃ alkyl represented by R¹ means methyl, ethyl, propyl,isopropyl, the C₁ to C₃ haloalkyl represented by R¹ includesbromomethyl, chloromethyl, fluoromethyl, dichloromethyl,trichloromethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl,1,1-difluoroethyl, 3,3,3-trifluoropropyl and the like, the C₁ to C₃alkyl represented by R²means methyl, ethyl, propyl, isopropyl,

[0017] the C₁ to C₆ alkyl represented by R⁵ includes methyl, ethyl,propyl, isopropyl, butyl, s-butyl, t-butyl and the like, the C₁ to C₆haloalkyl represented by R⁵ includes bromomethyl, chloromethyl,fluoromethyl, dichloromethyl, trichloromethyl, difluoromethyl,chlorodifluoromethyl, bromodifluoromethyl, trifluoromethyl,pentafluoroethyl, 2-fluoroethyl, 1,1-difluoroethyl,2,2,2-trichloroethyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl andthe like, the C₃ to C₆ alkenyl represented by R⁵ includes allyl,1-methylallyl, 1,1-dimethylallyl, 2-methylallyl, 1-butenyl, 2-butenyl,3-butenyl and the like, the C₃ to C₆ haloalkenyl represented by R⁵includes 1-chloroallyl, 1-bromoallyl, 2-chloroallyl, 3,3-dichloroallyland the like, the C₃ to C₆ alkynyl represented by R⁵ includes2-propynyl, 1-methyl-2-propynyl, 1,1-dimethyl-2-propynyl, 2-butynyl,3-butynyl, 1-methyl-2-butynyl and the like, the C₃ to C₆ haloalkynylrepresented by R⁵ includes 3-chloro-2-propynyl, 3-bromo-2-propynyl,1-fluoro-2-propynyl, 1-chloro-2-propynyl, 1-bromo-2-propynyl,1-chloro-2-butynyl and the like,

[0018] the C₁ to C₆ alkyl represented by R¹⁸ includes methyl, ethyl,propyl, isopropyl, butyl, s-butyl, t-butyl and the like,

[0019] the halogen represented by X¹ means fluorine, chlorine, bromine,iodine,

[0020] the halogen represented by X² means fluorine, chlorine, bromine,iodine,

[0021] the halogen represented by X³ and X⁴ means fluorine, chlorine,bromine, iodine,

[0022] the C₁ to C₆ alkyl represented by X³ and X⁴ includes methyl,ethyl, propyl, isopropyl, butyl, s-butyl, t-butyl and the like, the C₁to C₆ haloalkyl represented by X³ and X⁴ includes bromomethyl,chloromethyl, fluoromethyl, dichloromethyl, trichloromethyl,difluoromethyl, chlorodifluoromethyl, bromodifluoromethyl,trifluoromethyl, pentafluoroethyl, 2-fluoroethyl, 1,1-difluoroethyl,2,2,2-trichloroethyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl andthe like, the C₃ to C₆ alkenyl represented by X³ and X⁴ includes allyl,1-methylallyl, 1, 1-dimethylallyl, 2-methylallyl, 1-butenyl, 2-butenyl,3-butenyl and the like, the C₃ to C₆ haloalkenyl represented by X³ andX⁴ includes 1-chloroallyl, 1-bromoallyl, 2-chloroallyl,3,3-dichloroallyl and the like, the C₃ to C₆ alkynyl represented by X³and X⁴ includes 2-propynyl, 1-methyl-2-propynyl,1,1-dimethyl-2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-butynyl andthe like, the C₃ to C₆ haloalkynyl represented by X³ and X⁴ includes3-chloro-2-propynyl, 3-bromo-2-propynyl, 1-fluoro-2-propynyl,1-chloro-2-propynyl, 1-bromo-2-propynyl, 1-chloro-2-butynyl and thelike, the C₁ to C₆ alkoxy C₁ to C₆ alkyl represented by X³ and X⁴includes methoxymethyl, 2-methoxyethyl, 1-methoxyethyl, 3-methoxypropyl,ethoxymethyl, 2-ethoxyethyl, 3-ethoxypropyl, isopropoxymethyl,2-isopropoxyethyl and the like, the C₁ to C₆ alkoxy represented by X³and X⁴ includes methoxy, ethoxy, propoxy, isopropoxy, butoxy, s-butoxy,t-butoxy and the like, the C₁ to C₆ haloalkoxy represented by X³ and X⁴includes chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy,trifluoromethoxy, 2-fluoroethoxy, 2,2,2-trichloroethoxy and the like,the C₁ to C₆ alkoxycarbonyl C₁ to C₆ alkoxy represented by X³ and X⁴includes methoxycarbonylmethoxy, ethoxycarbonylmethoxy group,1-methoxycarbonylethoxy, 1-ethoxycarbonylethoxy,2-methoxycarbonylethoxy, 2-ethoxycarbonylethoxy and the like.

[0023] In the present compounds, those are preferable wherein R¹ ismethyl substituted with fluorine atom(s) such as trifluoromethyl,difluoromethyl and the like, or ethyl substituted with fluorine atom(s)such as pentafluoroethyl, 1,1-difluoroethyl and the like, morepreferably trifluoromethyl, R² is methyl or ethyl, more preferablymethyl, R⁵ is C₁ to C₃ alkyl such as methyl, ethyl and propyl, morepreferably methyl or ethyl, X¹ is halogen, more preferably chlorine, X²is halogen, more preferably fluorine, X³ is hydrogen, X⁴ is hydrogen, Wis oxgen, and/or Y is oxgen, from the standpoint of herbicidal activity.The substitution position of W on the benzen ring is preferably orthoposition of Y, at this situation, R⁴ is preferably hydrogen or methyl,more preferably hydrogen.

[0024] As the specially prefered compounds, compound wherein R¹ istrifluoromethyl, R² is methyl, R⁴ is hydrogen, R⁵ is methyl, X¹ ischlorine, X² is fluorine, X³ is hydrogen, X⁴ is hydrogen, W is oxgen, Yis oxgen, and the substitution position of W on the benzen ring is orthoposition of Y; and compound wherein R¹ is trifluoromethyl, R² is methyl,R⁴ is hydrogen, R⁵ is ethyl, X¹ is chlorine, X² is fluorine, X³ ishydrogen, X⁴ is hydrogen, W is oxgen, Y is oxgen, and the substitutionposition of W on the benzen ring is ortho position of Y are listed.

[0025] In the present compounds, geometrical isomers derived from adouble bond, optical isomers derived from asymmetric carbon, and adiastereomer may sometimes present, and the present compound alsoincludes isomers thereof and mixtures of them.

[0026] Then, methods for producing the present compounds will beillustrated.

[0027] The present compounds can be produced, for example, by thefollowing production methods ((Production Method 1) to (ProductionMethod 6)).

(Production Method 1)

[0028] The present compound can be produced by reacting a compound [III]of the formula [III]

[0029] wherein, R¹, R², W, Y, X¹, X², X³ and X⁴ are the same as definedabove,

[0030] with a compound [IV] of the formula [IV]

[0031] wherein, R⁴, and R⁵are the same as defined above, R⁶ represents aleaving group such as chlorine, bromine, iodine, methanesulfonyloxy,p-toluenesulfonyloxy and the like, in the presence of a base.

[0032] This reaction is conducted usually in a solvent, and the reactiontemperature is usually from 0 to 200° C., preferably 20 to 100° C., andthe reaction time is usually from an instant to 72 hours.

[0033] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the compound [IV] is 1 mol and theamount of the base is 1 mol based on 1 mol of the compound [III], andthe amounts thereof can be changed optionally depending on the reactioncondition.

[0034] The base to be used includes organic bases such as pyridine,quinoline, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-en,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine,diisopropylethylamine and the like, and inorganic bases such as lithiumcarbonate, sodium carbonate, potassium carbonate, calcium carbonate,barium carbonate, sodium hydrogen carbonate, potassium hydrogencarbonate, sodium hydride, potassium hydride, lithium hydroxide and thelike.

[0035] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether andthe like; aromatic hydrocarbons such as benzene, toluene, xylene and thelike; aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;ketones such as acetone, 2-butanone, methyl isobutyl ketone and thelike; esters such as ethyl formate, ethyl acetate, butyl acetate,diethyl carbonate and the like; nitro compounds such as nitromethane,nitrobenzene and the like; nitriles such as acetonitrile,isobutyronitrile and the like; acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfurcompounds such as dimethyl sulfoxide, sulfolane and the like; ormixtures thereof.

[0036] After completion of the reaction, the intended present compoundcan be obtained, for example, by the following operation 1) or 2).

[0037] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0038] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0039] Further, the resulted present compound can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0040] (Production Method 2)

[0041] Of the present compounds, the compound [I] wherein W is oxygencan be produced by reacting a compound [V] of the formula [V]

[0042] wherein, R¹, R², Y, X¹, X², X³ and X⁴ are the same as definedabove,

[0043] with an alcohol compound [VI] of the formula [VI]

[0044] wherein, R⁴, and R⁵ are the same as defined above, in thepresence of a dehydrating reagent.

[0045] This reaction is conducted usually in a solvent, and the reactiontemperature is usually from −20 to 150° C., preferably from 0 to 100°C., and the reaction time is usually from an instant to 48 hours.

[0046] As the dehydrating reagent, there are listed combinations oftriarylphosphines such as triphenylphosphine and the like ortrialkylphosphines such as triethylphosphine and the like, and, di(loweralkyl)azodicarboxylates such as diethylazodicarboxylate,diisopropylazodicarboxylate and the like.

[0047] Regarding the amounts of reagents to be used in the reaction, theamount of the alcohol compound [VI] is 1 to 3 mol, preferably 1 to 1.5mol, the amount of the triarylphosphine or trialkylphosphine is 1 to 3mol, preferably 1 to 1.5 mol, and the amount of the di(lower alkyl)azodicarboxylate is 1 to 3 mol, preferably 1 to 1.2 mol. based on 1 molof the compound [V]. The ratio of these reagents can be changedoptionally depending on the reaction condition.

[0048] The solvent to be used in the reaction includes aliphatichydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane,petroleum ether and the like; aromatic hydrocarbons such as benzene,toluene, xylene and the like; aromatic halogenated hydrocarbons such aschlorobenzene, dichlorobenzene, benzotrifluoride and the like; etherssuch as diethyl ether, diisopropyl ether, dioxane, THF, ethylene glycoldimethyl ether, diglyme and the like; or mixtures thereof.

[0049] After completion of the reaction, the intended present compoundcan be obtained, for example, by the following operation 1) or 2).

[0050] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated, and the residue is subjected to chromatography.

[0051] 2) A reaction solution is concentrated itself, and the residue issubjected to chromatography.

[0052] Further, the resulted present compound can also be purified by aprocedure such as re-crystallization and the like.

[0053] (Production Method 3)

[0054] A compound of the present invention can be produced by using acarboxylic acid compound [VII] of the formula [VII]

[0055] wherein, R¹, R², R⁴, W, Y, X¹, X², X³, and X⁴ are the same asdefined above,

[0056] and an alcohol compound [VIII] of the formula [VIII]

[0057] wherein, R⁵ is the same as defined above.

[0058] This reaction is conducted by, for example, reacting thecarboxylic acid compound [VII] with a chlorinating agent to give an acidchloride (hereinafter, referred to as <Process 3-1>), then, reacting theacid chloride and the compound [VIII] in the presence of a base(hereinafter, referred to as <Process 3-2>).

[0059] <Process 3-1>

[0060] This reaction is conducted in the absence of a solvent or in asolvent, and the reaction temperature is usually from 0 to 150° C., andthe reaction time is usually from an instant to 24 hours.

[0061] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the chlorinating agent is 1 mol basedon 1 mol of the carboxylic acid compound [VII], and the amounts thereofcan be changed optionally depending on the reaction condition.

[0062] Examples of the chlorinating agent to be used include thionylchloride, sulfuryl chloride, phosgene, oxalyl chloride, phosphorustrichloride, phosphorus pentachloride, phosphorus oxychloride and thelike.

[0063] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, nonane, decane, ligroin, cyclohexane,petroleum ether and the like; aromatic hydrocarbons such as benzene,toluene, xylene, mesitylene and the like; aliphatic halogenatedhydrocarbons such as methylene chloride, chloroform, carbontetrachloride, 1,2-dichloroethane, 1,2,3-trichloropropane and the like;aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, 1,4-dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;or mixtures thereof.

[0064] After completion of the reaction, for example, the reactionsolution is concentrated, and the residue is used itself in <Process3-2>.

[0065] <Process 3-2>

[0066] This reaction is conducted in the absence of a solvent or in asolvent, and the reaction temperature is usually from −20 to 100° C.,and the reaction time is usually from an instant to 24 hours.

[0067] Regarding the amounts of reagents to be used in the reaction, itis theoretical that each amount of the alcohol compound [VIII] and thebase is 1 mol based on 1 mol of the carboxylic acid compound [VII] usedin <Process 3-1>, and the amounts thereof can be changed optionallydepending on the reaction condition.

[0068] Examples of the base to be used include inorganic bases such assodium hydrogen carbonate, potassium hydrogen carbonate, lithiumcarbonate, sodium carbonate, potassium carbonate and the like,nitrogen-containing aromatic compounds such as pyridine, quinoline,4-dimethylaminopyridine, 2-picoline, 3-picoline, 4-picoline,2,3-lutidine, 2,4-lutidine, 2,5-lutidine, 2,6-lutidine, 3,4-lutidine,3,5-lutidine, 3-chloropyridine, 2-ethyl-3-methylpyridine,5-ethyl-2-methylpyridine and the like, tertiary amines such astriethylamine, diisopropylethylamine, tri-n-propylamine,tri-n-butylamine, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane and thelike.

[0069] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, nonane, decane, ligroin, cyclohexane,petroleum ether and the like; aromatic hydrocarbons such as benzene,toluene, xylene, mesitylene and the like; aliphatic halogenatedhydrocarbons such as methylene chloride, chloroform, carbontetrachloride, 1,2-dichloroethane, 1,2,3-trichloropropane and the like;aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, 1,4-dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;or mixtures thereof.

[0070] After completion of the reaction, the intended present compoundcan be obtained, for example, by the following operation 1) or 2).

[0071] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0072] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0073] Further, the resulted present compound can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0074] This reaction is not limited to the above-mentioned methods, andcan also be conducted by a method in which a reaction is conducted inthe presence of a condensing agent such as 1,1′-carbonyldiimidazole,1,3-dicyclohexylcarbodiimide and the like, a method in which a reactionis conducted in the presence of an acid catalyst, and other knownmethods.

[0075] (Production Method 4)

[0076] Of the present compounds, the compound [I] wherein X¹ is nitro orcyano can be produced by reacting an uracil compound [IX] of the formula[IX]

[0077] wherein, R¹, R² and X² are the same as defined above, R⁷represents fluorine, chlorine, bromine or iodine, and X¹¹ representsnitro or cyano,

[0078] with a compound [X] of the formula [X]

[0079] wherein, R⁴, R⁵, W, Y, X³, and X⁴ are the same as definedabove.]in the presence of a base.

[0080] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is from 0 to 200° C., and thereaction time is usually from an instant to 24 hours.

[0081] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the compound [X] is 1 mol and theamount of the base is 1 mol based on 1 mol of the uracil compound [IX],and the amounts thereof can be changed optionally depending on thereaction condition.

[0082] The base to be used includes organic bases such as pyridine,quinoline, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-en,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine,diisopropylethylamine and the like, and inorganic bases such as lithiumcarbonate, sodium carbonate, potassium carbonate, calcium carbonate,barium carbonate, sodium hydrogen carbonate, potassium hydrogencarbonate, sodium hydride, potassium hydride, lithium hydroxide, sodiumhydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide andthe like.

[0083] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether andthe like; aromatic hydrocarbons such as benzene, toluene, xylene and thelike; aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;ketones such as acetone, 2-butanone, methyl isobutyl ketone and thelike; esters such as ethyl formate, ethyl acetate, butyl acetate,diethyl carbonate and the like; nitro compounds such as nitromethane,nitrobenzene and the like; nitriles such as acetonitrile,isobutyronitrile and the like; acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfurcompounds such as dimethyl sulfoxide, sulfolane and the like; ormixtures thereof.

[0084] This reaction may sometimes be accelerated by using a catalyst.As the catalyst, copper iodide, copper bromide, copper chloride, copperpowder and the like are listed, and the amount of the catalyst used inthe reaction is from 0.0001 to 0.1 mol based on 1 mol of the uracilcompound [IX], and the amounts thereof can be changed optionallydepending on the reaction condition.

[0085] After completion of the reaction, the intended present compoundcan be obtained, for example, by the following operation 1) or 2).

[0086] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0087] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0088] Further, the resulted present compound can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0089] (Production Method 5)

[0090] Of the present compounds, the compound [I] wherein X¹ isfluorine, chlorine, bromine or iodine can be produced by the followingscheme.

[0091] wherein, R¹, R², R⁴, R⁵, W, X², X³, and X⁴ are the same asdefined above, X¹² represents fluorine, chlorine, bromine or iodine, andY¹ represents oxygen, sulfur, imino or alkylimino. <Process 5-1>: Aprocess for producing the compound [XII] from the compound [XI].

[0092] The compound [XII] can be produced, for example, by reducing thecompound [XI] using an iron powder in the presence of an acid in asolvent.

[0093] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is usually from 0 to 200° C.,preferably from room temperature to the reflux temperature. The reactiontime is usually from an instant to 24 hours.

[0094] Regarding the amounts of reagents to be used in the reaction, theamount of the iron powder is from 3 mol to excess and the amount of theacid is 1 to 10 mol based on 1 mol of the compound [XI], and the amountsthereof can be changed optionally depending on the reaction condition.

[0095] As the acid to be used, acetic acid and the like are listed.

[0096] As the solvent to be used, there are listed, for example, water,acetic acid, ethyl acetate and the like or mixtures thereof.

[0097] After completion of the reaction, an intended material can beobtained by a usual post-treatment operation such as by filtrating,then, pouring a reaction solution into water and the deposited crystalsare collected by filtration, or, extracting with an organic solvent,neutralization, concentration and the like.

[0098] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0099] <Process 5-2>: A Process for Producing the Compound [XIII] fromthe Compound [XII].

[0100] The compound [XIII] can be produced by i) diazotizing thecompound [XII] in a solvent, then, ii) subsequently, reacting the diazocompound with potassium iodide, copper [I] bromide, copper [I] chlorideor a mixture of hydrofluoric acid with boric acid (hereinafter, referredto as hydroborofluoric acid) depending on the intended compound, in asolvent.

[0101] In the diazotization reaction of the first step, the reactiontemperature is usually from −20 to 20° C., and the reaction time isusually from an instant to 5 hours.

[0102] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the diazotization agent is 1 mol basedon 1 mol of the compound [XII], and the amounts thereof can be changedoptionally depending on the reaction condition.

[0103] As the diazotization agent to be used, nitrites such as sodiumnitrite, potassium nitrite, isoamyl nitrite, t-butyl nitrite and thelike, are listed.

[0104] As the solvent to be used, there are listed, for example,acetonitrile, hydrobromic acid, hydrochloric acid, sulfuric acid, waterand the like or mixtures thereof.

[0105] The reaction solution after completion of the reaction is used asit is in the following reaction.

[0106] In the reaction of the second step, the reaction temperature isfrom 0 to 80° C., and the reaction time is usually from an instant to 24hours.

[0107] Regarding the amounts of reagents to be used in the reaction,each amount of potassium iodide, copper [I] bromide, copper [I] chlorideor hydroborofluoric acid is from 1 to 3 mol based on 1 mol of thecompound [XII], and the amounts thereof can be changed optionallydepending on the reaction condition.

[0108] When copper [I] bromide is used, the reaction can also beconducted in the presence of copper [II] bromide, and when copper [I]chloride is used, the reaction can also be conducted in the presence ofcopper [II] chloride.

[0109] As the solvent to be used, there are listed, for example,acetonitrile, diethyl ether, t-butyl methyl ether, hydrobromic acid,hydrochloric acid, sulfuric acid water and the like or mixtures thereof.

[0110] After completion of the reaction, an intended present compoundcan be obtained, for example, by the following operation 1) or 2).

[0111] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0112] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0113] Further, the resulted present compound can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0114] (see, Org. Syn. Coll. Vol. 2, 604 (1943), Vol. 1, 136 (1932)).

[0115] Further, this reaction is not limited to the above-mentionedmethods, and production can also be conducted by reacting the compound[XII] with a diazotizing agent in a solvent in the presence of potassiumiodide, copper [I] bromide, copper [I] chloride or hydroborofluoric aciddepending on the intended compound (see, Heterocycles., 38, 1581 (1994),and the like).

[0116] When copper [I] bromide is used, the reaction can also beconducted in the presence of copper [II] bromide, and when copper [I ]chloride is used, the reaction can also be conducted in the presence ofcopper [II] chloride.

[0117] (Production Method 6)

[0118] The present compound can be produced by reacting an uracilcompound [XXXI] of the formula [XXXI]

[0119] wherein, R¹, R⁴, R⁵, W, Y, X¹, X², X³, and X⁴ are the same asdefined above,

[0120] with a compound [XXXX] of the formula [XXXX]

[0121] wherein, R¹⁸ represents a leaving group such as chlorine,bromine, iodine, methanesulfonyloxy, p-toluenesulfonyloxy and the like,and R² is the same as defined above, in the presence of a base.

[0122] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is usually from 0 to 200C,preferable 20 to 100° C., and the reaction time is usually from aninstant to 24 hours.

[0123] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the compound [XXXX] is 1 mol and theamount of the base is 1 mol based on 1 mol of the uracil compound[XXXI], and the amounts thereof can be changed optionally depending onthe reaction condition.

[0124] The base to be used includes organic bases such as pyridine,quinoline, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-en,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine,diisopropylethylamine and the like, metal alkoxides such as sodiummethoxide, sodium ethoxide, potassium t-butoxide and the like, andinorganic bases such as lithium carbonate, sodium carbonate, potassiumcarbonate, calcium carbonate, barium carbonate, sodium hydrogencarbonate, potassium hydrogen carbonate, sodium hydride, potassiumhydride, lithium hydroxide, sodium hydroxide, potassium hydroxide,calcium hydroxide, barium hydroxide and the like.

[0125] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether andthe like; aromatic hydrocarbons such as benzene, toluene, xylene and thelike; aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;ketones such as acetone, 2-butanone, methyl isobutyl ketone and thelike; esters such as ethyl formate, ethyl acetate, butyl acetate,diethyl carbonate and the like; nitro compounds such as nitromethane,nitrobenzene and the like; nitriles such as acetonitrile,isobutyronitrile and the like; acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfurcompounds such as dimethyl sulfoxide, sulfolane and the like; alcoholssuch as methanol, ethanol, ethylene glycol, isopropanol, t-butanol andthe like; or mixtures thereof.

[0126] After completion of the reaction, an intended present compoundcan be obtained, for example, by the following operation 1) or 2).

[0127] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0128] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0129] Further, the resulted present compound can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0130] The compound [IV], the alcohol compound [VI], the alcoholcompound [VIII] and the compound [X]used in the methods for producingthe present compound can be produced by known methods, or, commerciallyavailable materials are used.

[0131] The carboxylic acid compound [VII] can be produced by acidhydrolysis of the present compound [I].

[0132] Some of intermediates used in the method for producing thepresent compound can be produced, for example, by the followingproduction methods ((Intermediate Production Method 1) to (IntermediateProduction Method 16)).

[0133] (Intermediate Production Method 1)

[0134] Of compound [III], the compound wherein W and Y are oxygen orsulfur (i.e. compound [XIX]) and the compound [XIV] can also be producedby a method described in the following scheme.

[0135] Wherein, R¹, R², R⁷, X², X³, X⁴ and X¹² are the same as definedabove, each of R¹⁵ and R¹⁷ independently represents oxygen or sulfur,and R¹⁶ represents a protective group such as silyl group such ast-butyldimethylsilyl and the like; C₁ to C₆ alkyl which may besubstituted such as t-butyl, methyl and the like; benzyl which may besubstituted such as benzyl and the like; methoxymethyl, acetyl,methoxycarbonyl, ethoxycarbonyl and the like.

[0136] <Process A1-1>: A Process for Producing the Compound [XIV] fromthe Compound [XXXXI].

[0137] The compound [XIV] can be produced by reacting the compound[XXXXI] with the compound [XXXXII] in the presence of a base.

[0138] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is usually from 0 to 200° C.,and the reaction time is usually from an instant to 24 hours.

[0139] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the compound [XXXXII] is 1 mol and theamount of the base is 1 mol based on 1 mol of the compound [XXXXI], andthe amounts thereof can be changed optionally depending on the reactioncondition.

[0140] The base to be used includes organic bases such as pyridine,quinoline, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-en,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine,diisopropylethylamine and the like, and inorganic bases such as lithiumcarbonate, sodium carbonate, potassium carbonate, calcium carbonate,barium carbonate, sodium hydrogen carbonate, potassium hydrogencarbonate, sodium hydride, potassium hydride, and the like.

[0141] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether andthe like; aromatic hydrocarbons such as benzene, toluene, xylene and thelike; aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;ketones such as acetone, 2-butanone, methyl isobutyl ketone and thelike; esters such as ethyl formate, ethyl acetate, butyl acetate,diethyl carbonate and the like; nitro compounds such as nitromethane,nitrobenzene and the like; nitriles such as acetonitrile,isobutyronitrile and the like; acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfurcompounds such as dimethyl sulfoxide, sulfolane and the like; ormixtures thereof.

[0142] After completion of the reaction, an intended material can beobtained, for example, by the following operation 1), 2) or 3).

[0143] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0144] 2) The reaction mixture is poured into water and the depositedcrystals are collected by filtration.

[0145] 3) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0146] Further, the intended material can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0147] <Process A1-2>: A Process for Producing the Compound [XVI] fromthe Compound [XIV].

[0148] The compound [XVI] can be produced by reacting the compound [XIV]with the compound [XV] in the presence of a base.

[0149] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is usually from −20 to 200°C., preferable −5 to 80° C., and the reaction time is usually from aninstant to 24 hours.

[0150] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the compound [XV] is 1 mol and theamount of the base is 1 mol based on 1 mol of the compound [XIV], andthe amounts thereof can be changed optionally depending on the reactioncondition.

[0151] The base to be used includes organic bases such as pyridine,quinoline, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-en,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine,diisopropylethylamine and the like, and inorganic bases such as lithiumcarbonate, sodium carbonate, potassium carbonate, calcium carbonate,barium carbonate, sodium hydrogen carbonate, potassium hydrogencarbonate, sodium hydride, potassium hydride, lithium hydroxide, and thelike.

[0152] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether andthe like; aromatic hydrocarbons such as benzene, toluene, xylene and thelike; aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;ketones such as acetone, 2-butanone, methyl isobutyl ketone and thelike; esters such as ethyl formate, ethyl acetate, butyl acetate,diethyl carbonate and the like; nitro compounds such as nitromethane,nitrobenzene and the like; nitriles such as acetonitrile,isobutyronitrile and the like; acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfurcompounds such as dimethyl sulfoxide, sulfolane and the like; ormixtures thereof.

[0153] After completion of the reaction, an intended material can beobtained, for example, by the following operation 1) or 2).

[0154] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is washed withhydrochloric acid, then brine, dried and concentrated.

[0155] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0156] Further, the intended material can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0157] <Process A1-3>: A Process for Producing the Compound [XVII] fromthe Compound [XVI].

[0158] The compound [XVII] can be produced, for example, by reducing thecompound [XVI] using an iron powder in the presence of an acid in asolvent.

[0159] The reaction temperature is usually from 0 to 200° C., preferablyfrom room temperature to the reflux temperature. The reaction time isusually from an instant to 24 hours.

[0160] Regarding the amounts of reagents to be used in the reaction, theamount of the iron powder is from 3 mol to excess and the amount of theacid is 1 to 10 mol based on 1 mol of the compound [XVI], and theamounts thereof can be changed optionally depending on the reactioncondition.

[0161] As the acid to be used, acetic acid and the like are listed.

[0162] As the solvent to be used, there are listed, for example, water,acetic acid, ethyl acetate and the like or mixtures thereof.

[0163] After completion of the reaction, and intended material can beobtained by usual post-treatment such as by filtrating, then, pouring areaction solution into water and collecting the produced crystals byfiltration, or, subjecting a reaction solution to extraction with anorganic solvent, neutralization, concentration and the like.

[0164] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0165] <Process A1-4>: A Process for Producing the Compound [XVIII] fromthe Compound [XVII].

[0166] The compound [XVIII] can be produced by i) diazotizing thecompound [XVII] in a solvent, then, ii) subsequently, reacting the diazocompound with potassium iodide, copper (I) bromide, copper (I) chlorideor hydroborofluoric acid in a solvent.

[0167] In the diazotization reaction of the first step, the reactiontemperature is usually from −20 to 20%, and the reaction time is usuallyfrom an instant to 5 hours.

[0168] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the diazotization agent is 1 mol basedon 1 mol of a compound of the general formula [XVII], and the amountsthereof can be changed optionally depending on the reaction condition.

[0169] As the diazotization agent to be used, nitrites such as sodiumnitrite, potassium nitrite, isoamyl nitrite, t-butyl nitrite and thelike, are listed.

[0170] As the solvent to be used, there are listed, for example,acetonitrile, hydrobromic acid, hydrochloric acid, sulfuric acid, waterand the like or mixtures thereof.

[0171] The reaction solution after completion of the reaction is used asit is in the following reaction.

[0172] In the reaction of the second step, the reaction temperature isfrom 0 to 80° C., and the reaction time is usually from an instant to 24hours.

[0173] Regarding the amounts of reagents to be used in the reaction,each amount of potassium iodide, copper (I) bromide, copper (I) chlorideor hydroborofluoric acid is from 1 to 3 mol based on 1 mol of thecompound [XVII], and the amounts thereof can be changed optionallydepending on the reaction condition. When copper [I] bromide is used,the reaction can also be conducted in the presence of copper (II)bromide, and when copper (I) chloride is used, the reaction can also beconducted in the presence of copper (II) chloride.

[0174] As the solvent to be used, there are listed, for example,acetonitrile, diethyl ether, t-butyl methyl ether, hydrobromic acid,hydrochloric acid, sulfuric acid, water and the like or mixturesthereof.

[0175] After completion of the reaction, an intended material can beobtained by a usual post-treatment such as by collecting the producedcrystals by filtration (if necessary, by adding water), or, extractingwith an organic solvent, concentration and the like.

[0176] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0177] Further, this reaction is not limited to the above-mentionedmethods, also be conducted by reacting the compound [XVII] with adiazotizing agent in a solvent (for example, acetonitrile, diethylether, t-butyl methyl ether, hydrobromic acid, hydrochloric acid,sulfuric acid, water and the like or mixtures thereof) in the presenceof potassium iodide, copper (I) bromide, copper (I) chloride orhydroborofluoric acid.

[0178] (see, Heterocycles., 38, 1581 (1994), and the like).

[0179] <Process A1-5>: A Process for Producing the Compound [XIX] fromthe Compound [XVIII].

[0180] The compound [XIX] can be produced by de-protecting the compound[XVIII] using boron tribromide, HBr/acetic acid, conc. hydrochloricacid, conc. sulfuric acid or the like according to a method described inProtective Groups in Organic Synthesis (published by AWiley-Interscience publication).

[0181] Herein, in the case the compound [XVIII] wherein R¹⁶ is a benzylwhich may be substituted such as benzyl, the compound [XIX] can also beproduced by hydrogenation of the compound [XVIII] in the presence of acatalyst.

[0182] This reaction is usually conducted in a solvent. The reactiontemperature is usually from −20 to 150%, preferably from 0 to 50° C. Thereaction time is usually from an instant to 48 hours. This reaction canalso be conducted under positive pressure, and the reaction is usuallyconducted under a pressure of 1 to 5 atom.

[0183] The amount of the catalyst used in this reaction is from 0.001 to100% by weight based on the compound [XVIII].

[0184] As the catalyst to be used in the reaction, anhydrouspalladium/carbon, water-containing palladium/carbon, platinum oxide andthe like are listed.

[0185] The solvent includes carboxylic acids such as formic acid, aceticacid, propionic acid and the like, esters such as ethyl formate, ethylacetate, butyl acetate, diethyl carbonate and the like; ethers such as1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and thelike; alcohols such as methanol, ethanol, isopropanol, and the like;water, or mixtures thereof.

[0186] After completion of the reaction, an intended material can beobtained by a usual post-treatment operation such as by filtrating areaction solution before concentrating the solution, or, pouring areaction solution into water before filtrating the produced crystal, or,pouring a reaction solution into water and subjecting the resultedmixture to extraction with an organic solvent, concentration and thelike.

[0187] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0188] (Intermediate Production Method 2)

[0189] Of compounds [III], the compound wherein W is NH (i.e. compound[XXIII]) can also be produced by a method described in the followingscheme.

[0190] Wherein, R¹, R², R⁷, Y, X¹, X², X³ and X⁴ are the same as definedabove.

[0191] <Process A2-1>: A Process for Producing the Compound [XXII] fromthe Compound [XX]

[0192] The compound [XXII] can be produced by reacting the compound [XX]with the compound [XXI] in the presence of a base.

[0193] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is usually from 0 to 200° C.,and the reaction time is usually from an instant to 24 hours.

[0194] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the compound [XXI] is 1 mol and theamount of the base is 1 mol based on 1 mol of the compound [XX], and theamounts thereof can be changed optionally depending on the reactioncondition.

[0195] The base to be used includes organic bases such as pyridine,quinoline, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-en,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine,diisopropylethylamine and the like, and inorganic bases such as lithiumcarbonate, sodium carbonate, potassium carbonate, calcium carbonate,barium carbonate, sodium hydrogen carbonate, potassium hydrogencarbonate, sodium hydride, potassium hydride, lithium hydroxide, and thelike.

[0196] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether andthe like; aromatic hydrocarbons such as benzene, toluene, xylene and thelike; aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;ketones such as acetone, 2-butanone, methyl isobutyl ketone and thelike; esters such as ethyl formate, ethyl acetate, butyl acetate,diethyl carbonate and the like; nitro compounds such as nitromethane,nitrobenzene and the like; nitriles such as acetonitrile,isobutyronitrile and the like; acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfurcompounds such as dimethyl sulfoxide, sulfolane and the like; ormixtures thereof.

[0197] This reaction may sometimes be accelerated by adding a catalyst.

[0198] The amount of the catalyst used in the reaction is preferablyfrom 0.0001 to 0.1 mol based on 1 mol of the compound [XX], and theamounts thereof can be changed optionally depending on the reactioncondition.

[0199] As the catalyst, copper iodide, copper bromide, copper chloride,copper powder and the like are listed, After completion of the reaction,an intended material can be obtained, for example, by the followingoperation 1) or 2).

[0200] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0201] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0202] Further, the intended material can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0203] <Process A2-2>: A Process for Producing the Compound [XXIII] fromthe Compound [XXII]

[0204] The compound [XXIII] can be produced, for example, by reducingthe compound [XXII] using an iron powder in the presence of an acid in asolvent.

[0205] The reaction temperature is usually from 0 to 200° C., preferablyfrom room temperature to the reflux temperature. The reaction time isusually from an instant to 24 hours.

[0206] Regarding the amounts of reagents to be used in the reaction, theamount of the iron powder is from 3 mol to excess and the amount of theacid is 1 to 10 mol based on 1 mol of the compound [XXII], and theamounts thereof can be changed optionally depending on the reactioncondition.

[0207] As the acid to be used, acetic acid and the like are listed.

[0208] As the solvent to be used, there are listed, for example, water,acetic acid, ethyl acetate and the like or mixtures thereof.

[0209] After completion of the reaction, an intended material can beobtained by a usual post-treatment such as by filtrating, then,collecting the produced crystals by filtration (if necessary, by addingwater), or, extracting with an organic solvent, neutralization,concentration and the like.

[0210] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0211] (Intermediate Production Method 3)

[0212] Of compounds [III], the compound wherein W is oxygen (i.e.compound [V]) can be produced by a method described in the followingscheme.

[0213] Wherein, R¹, R², Y, X¹, X², X³ and X⁴ are the same as definedabove.

[0214] The compound [V] can be produced by i) reacting the compound[XXIII] with diazotizing agent in a solvent, then, ii) subsequently,heating the product in an acidic solvent, or, allowing a copper salt toact on the product in the presence of a copper catalyst.

[0215] In the reaction of the first step, the reaction temperature isusually from −20 to 10° C., and the reaction time is usually from aninstant to 5 hours.

[0216] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the diazotization agent is 1 mol basedon 1 mol of the compound [XXIII], and the amounts thereof can be changedoptionally depending on the reaction condition.

[0217] As the diazotization agent to be used, nitrites such as sodiumnitrite, potassium nitrite, isoamyl nitrite, t-butyl nitrite and thelike, are listed.

[0218] As the solvent to be used, there are listed, for example,acetonitrile, hydrochloric acid, hydrobromic acid, sulfuric acid, waterand the like or mixtures thereof.

[0219] The reaction solution after completion of the reaction is used asit is in the following reaction.

[0220] In the heating reaction in an acidic solvent of the second step,the reaction temperature is from 60° C. to reflux temperature, and thereaction time is usually from an instant to 48 hours.

[0221] As the acidic solvent there are listed, for example, hydrochloricacid, hydrobromic acid, sulfuric acid solution and the like or mixturesthereof.

[0222] After completion of the reaction, an intended material can beobtained by usual post-treatment such as by collecting the producedcrystals by filtration (if necessary, by adding water), or, extractingwith an organic solvent, concentration and the like.

[0223] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0224] The reaction for allowing a copper salt to act in the presence ofa copper catalyst in the second step is conducted in a solvent. Thereaction temperature is from 0° C. to reflux temperature, and thereaction time is from an instant to 24 hours.

[0225] Regarding the amounts of reagents to be used in the reaction, theamount of the copper catalyst is 0.001 to 5 mol and the amount of thecopper salt is 1 to 100 mol based on 1 mol of the compound [XXIII], andthe amounts thereof can be changed optionally depending on the reactioncondition.

[0226] As the copper catalyst to be used, copper (I) oxide and the likeare listed, and as the copper salt, copper (II) sulfate, copper (II)nitrate and the like are listed.

[0227] As the solvent, there are listed, for example, water,hydrochloric acid, sulfuric acid and the like or mixtures thereof.

[0228] After completion of the reaction, an intended material can beobtained by a usual post-treatment such as by extracting with an organicsolvent, concentration and the like.

[0229] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0230] (Intermediate Production Method 4)

[0231] The compound [IX] can be produced by a method described in thefollowing scheme.

[0232] Wherein, R¹, R², R⁷, X², and X¹¹ are the same as defined above.

[0233] The compound [IX] can be produced by diazotizing the compound[XXIV] in a solvent, then, subsequently reacting the diazo compound witha halogenating agent.

[0234] <The First Step(Diazotization Reaction)>

[0235] reaction temperature: from −20 to 20° C.

[0236] reaction time: from an instant to 5 hours

[0237] the amount of the diazotizing agent: from 1 mol to excess basedon 1 mol of compound [XXIV]

[0238] diazotizing agent: nitrites such as sodium nitrite, isoamylnitrite, t-butyl nitrite and the like

[0239] Solvent: acetonitrile, hydrochloric acid and the like

[0240] <The Second Step>

[0241] reaction temperature: from 0 to 80° C.

[0242] reaction time: from an instant to 24 hours the amounts of thehalogenating reagent: from 1 to 3 mol based on 1 mol of compound [XXIV]

[0243] halogenating reagent: potassium iodide, copper [I] bromide,copper [I] chloride or hydroborofluoric acid and the like

[0244] Solvent: acetonitrile, hydrochloric acid and the like

[0245] The compound [IX] can also be produced by reacting the compound[XXIV] with a diazotizing agent in a solvent in the presence of ahalogenating agent.

[0246] reaction temperature: from 0 to 80° C.

[0247] reaction time: from an instant to 48 hours

[0248] the amount of the diazotizing agent: from 1 mol to excess basedon 1 mol of compound [XXIV]

[0249] diazotizing agent: nitrites such as isoamyl nitrite, t-butylnitrite and the like

[0250] the amounts of the halogenating reagent: from 1 to 3 mol based on1 mol of compound [XXIV]

[0251] halogenating reagent: potassium iodide, copper [I] bromide,copper [I] chloride or hydroborofluoric acid and the like

[0252] Solvent: acetonitrile and the like

[0253] When copper [I] bromide is used, the reaction can also beconducted in the presence of copper [II] bromide, and when copper [I]chloride is used, the reaction can also be conducted in the presence ofcopper [II] chloride.

[0254] (Intermediate Production Method 5)

[0255] Of compounds [X], the compound wherein W is oxygen or sulfur(i.e. compound [XXVI]) can be produced by a method described in thefollowing scheme.

[0256] Wherein, R⁴, R⁵, R⁶, R¹⁵, Y, X³ and X⁴ are the same as definedabove.

[0257] The compound [XXVI] can be produced by reacting the compound[XXV] with the compound [IV] in a solvent in the presence of a base.

[0258] reaction temperature: from 0 to 200° C.

[0259] reaction time: from an instant to 72 hours

[0260] amount of compound [IV]: 1 to 3 mol based on 1 mol of compound[XXV]

[0261] amount of a base: 1 to 3 mol based on 1 mol of compound [XXV]

[0262] base: triethylamine, potassium carbonate, sodium hydride and thelike solvent: tetrahydrofuran, acetonitrile, N,N-dimethylformamide,dimethyl sulfoxide, methanol, water and the like; or mixtures thereof

[0263] (Intermediate Production Method 6)

[0264] Of compounds [X], the compound wherein Y is oxygen or sulfur(i.e. compound [XXX]) can be produced by a method described in thefollowing scheme.

[0265] Wherein, R⁴, R⁵, R⁶, R¹⁶ R¹⁷ W, n, X³ and X⁴ have the samemeanings as described above.

[0266] <Process A6-1>: A Process for Producing the Compound [XXVIII]from the Compound [XXVII]

[0267] The compound [XXVIII] can be produced by reacting the compound[XXVII] with t-butyldimethylsilyl chloride, isobutene, benzyl chloride,benzyl bromide and the like (see, Protective Groups in Organic Synthesis(A Wiley-Interscience publication)).

[0268] <Process A6-2>: A Process for Producing the Compound [XXIX] fromthe Compound [XXVIII]

[0269] The compound [XXIX] can be produced by reacting the compound[XXVIII] with the compound [IV] in a solvent in the presence of a base.

[0270] reaction temperature: from 0 to 200° C.

[0271] reaction time: from an instant to 72 hours

[0272] amount of compound [IV]: 1 to 3 mol based on 1 mol of compound[XXVIII]

[0273] amount of a base: 1 to 3 mol based on 1 mol of compound [XXVIII]

[0274] base: triethylamine, potassium carbonate, sodium hydride and thelike solvent: tetrahydrofuran, acetonitrile, N,N-dimethylformamide,dimethyl sulfoxide, methanol, water and the like; or mixtures thereof

[0275] <Process A6-3>: A Process for Producing the Compound [XXX] fromthe Compound [XXIX]

[0276] The compound [XXX] can be produced by de-protection of thecompound [XXIX] according to a method described in “Yuki Kagaku Jikkenno Tebiki (published by Manual of Organic Chemical Experiment)”, vol. 4,(published by Kagaku Dojin sha), Protective Groups in Organic Synthesis(A Wiley-Interscience publication). Specifically, the compound [XXIX]wherein R¹⁸ is silyl such as t-butyldimethylsilyl and the like can bede-protected by reacting trifluoroacetic acid or tetrabutylammoniumfluoride and the like in a solvent such as methylene chloride, ethylacetate, water or the like. The compound [XXIX] wherein R¹⁸ is benzylwhich may be substituted such as benzyl and the like can be de-protectedby reacting with hydrogen in the presence of a catalyst.

[0277] reaction temperature: −20 to 150° C., preferably from 0 to 50° C.

[0278] reaction time:from an instant to 48 hours

[0279] amount of the catalyst: from 0.001 to 100% by weight based on thecompound [XXIX]

[0280] catalyst: anhydrous palladium/carbon, water-containingpalladium/carbon, platinum oxide and the like

[0281] solvent: acetic acid, ethyl acetate, methanol and the like

[0282] (Intermediate Production Method 7)

[0283] Of compounds [XXXI], the compound wherein Y is oxygen or sulfurcan be produced by a method described in the following scheme.

[0284] Wherein, R¹, R⁴, R⁵, R⁷, R¹⁷, W, X¹, X², X³ and X⁴ are the sameas defined above, R¹⁸ represents C₁ to C₆ alkyl (for example, methyl,ethyl and the like) or phenyl, R¹⁹ represents C₁ to C₆ alkyl (forexample, methyl, ethyl and the like).

[0285] <Process A7-1>: A Process for Producing the Compound [XXXII] fromthe Compound [XXXVI]

[0286] The compound [XXXII] can be produced by converting the compound[XXXVI] into the compound [XXXVII], then reacting with the compound[XXXVIII] (see, Bioorganic and Medicinal Chemistry Letters, vol. 5, p.1035, (1995).

[0287] <Process A7-2>: A Process for Producing the Compound [XXXIII]from the Compound [XXXII]

[0288] The compound [XXXIII] can be produced by a method according to aknown method described in U.S. Pat. No. 4,859,229 and the like from thecompound [XXXII].

[0289] Specifically, the compound [XXXIII] can be produced byisocyanating the compound [XXXII] in a solvent or in the absence of asolvent.

[0290] Isocyanating agent: phosgene, trichloromethyl chloroformate,oxalyl chloride and the like

[0291] Amount of isocyanating agent: from 1 mol to excess based on 1 molof the compound [XXXII]

[0292] Solvent: aromatic hydrocarbons such as benzene, toluene and thelike, halogenated aromatic hydrocarbons such as chlorobenzene and thelike, esters such as ethyl acetate and the like

[0293] Reaction Temperature: from room temperature to reflux temperature

[0294] Reaction Time: from an instant to 48 hours

[0295] After completion of the reaction, an intended material can beobtained by concentrating a reaction solution itself, and the like. Thiscompound can also be purified by an operation such as re-crystallizationand the like.

[0296] <Process A7-3>: A Process for Producing the Compound [XXXIV] fromthe Compound [XXXII]

[0297] The compound [XXXIV] can be produced by a method according to aknown method described in U.S. Pat. No. 4,879,229 and the like from thecompound [XXXII].

[0298] Specifically, the compound [XXXIV] can be produced by reactingthe compound [XXXII] with a compound [b-4] of the formula [b-4]

[0299] wherein, R¹⁸ and X¹² are the same as defined above, in thepresence of a base.

[0300] This reaction is usually conducted in a solvent, and also can beconducted in the absence of a solvent. The reaction temperature isusually from −20 to 200° C. The reaction time is usually from an instantto 48 hours.

[0301] The amount of the compound [b-4] used in the reaction is from 0.5mol to excess, preferably from 1.0 to 1.2 mol based on 1 mol of thecompound [XXXII].

[0302] The amount of the base used in the reaction is from 0.5 mol toexcess, preferably from 1.0 to 1.2 mol based on 1 mol of the compound[XXXII].

[0303] The base includes inorganic bases such as sodium carbonate,sodium hydroxide and the like, organic bases such as pyridine,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, diisopropylethylamine and the like.

[0304] The solvent include aliphatic halogenated hydrocarbons such aschloroform and the like, ethers such as tetrahydrofuran, 1,4-dioxane andthe like, nitrites such as acetonitrile and the like, esters such asethyl acetate, water or mixtures thereof, and the like.

[0305] After completion of the reaction, an intended material can beobtained by a usual post-treatment operation such as by filtrating thereaction solution before concentrating the solution itself, or, pouringthe reaction solution into water and collecting the produced crystals byfiltration, or, pouring the reaction solution into water and subjectingthe mixture to extraction with an organic solvent, concentration and thelike. This compound can also be purified by an operation such asre-crystallization, chromatography and the like.

[0306] <Process A7-4>: A Process for Producing the Compound [XXXIX] fromthe Compound [XXXIII]

[0307] The compound [XXXIX] can be produced by a method according to aknown method described in U.S. Pat. No. 4,879,229 and the like from thecompound [XXXIII] and the compound [XXXV].

[0308] Specifically, the compound [XXXIX] can be produced by reactingthe compound [XXXIII] with the compound [XXXV] in a solvent in thepresence of a base.

[0309] Amount of the compound [XXXV]: 0.5 mol to excess, preferably from0.8 to 1.2 mol based on 1 mol of the compound [XXXIII]

[0310] Base: inorganic bases such as sodium hydride and the like, metalalkoxides such as sodium methoxide, sodium ethoxide and the like

[0311] Amount of a base: 0.5 mol to excess, preferably from 0.8 to 1.2mol based on 1 mol of a compound of the general formula [XXXIII]

[0312] Solvent: aromatic hydrocarbons such as benzene, toluene and thelike; halogenated aromatic hydrocarbons such as chlorobenzene and thelike; amides such as N,N-dimethylformamide and the like; ethers such astetrahydrofuran and the like; halogenated aliphatic hydrocarbons such aschloroform and the like; sulfur compounds such as dimethyl sulfoxide andthe like; and mixtures thereof

[0313] Reaction temperature: −40° C. to solvent reflux temperature

[0314] Reaction time: instant to 72 hours

[0315] After completion of the reaction, an intended material can beobtained by a post-treatment operation such as by filtrating a reactionsolution before concentrating the solution itself, or, adding an acid toa reaction solution and collecting the produced crystals by filtration,or, adding an acid to a reaction solution, then, subjecting the mixtureto extraction with an organic solvent, concentration and the like. Asthe acid to be added, hydrochloric acid, acetic acid, trifluoroaceticacid, p-toluenesulfonic acid, or aqueous solutions thereof and the like.This compound can also be purified by an operation such asre-crystallization, chromatography and the like.

[0316] The resulted compound [XXXIX] can also be reacted with thecompound [XXXX] according to a method described in (Production Method 6)without conducting post-treatment such as isolation and the like, toproduce the present compound.

[0317] <Process A7-5>: A Process for Producing the Compound [XXXIX] fromthe Compound [XXXIV]

[0318] The compound [XXXIX] can be produced by a method according to aknown method described in U.S. Pat. No. 4,879,229 and the like from thecompound [XXXIV] and the compound [XXXV].

[0319] Specifically, the compound [XXXIX] can be produced by reactingthe compound [XXXIV] with the compound [XXXV] in the presence of a base.

[0320] This reaction is usually conducted in a solvent, and the reactiontemperature is usually from −20 to 200° C., preferably from 0 to 130° C.The reaction time is usually from an instant to 72 hours.

[0321] The amount of the compound [XXXV] used in the reaction is from0.5 mol to excess, preferably from 0.8 to 1.2 mol based on 1 mol of thecompound [XXXIV].

[0322] The amount of the base used in the reaction is from 0.5 mol toexcess, preferably from 0.8 to 1.2 mol based on the compound [XXXIV].

[0323] The base includes organic bases such as 4-dimethylaminopyridine,diisopropylethylamine and the like, inorganic bases such as sodiumcarbonate, potassium carbonate, sodium hydride, potassium hydride andthe like, metal alkoxides such as sodium methoxide, sodium ethoxide,potassium t-butoxide and the like.

[0324] The solvent includes ketones such as acetone, methyl isobutylketone and the like; aliphatic hydrocarbons such as hexane, heptane,petroleum ether and the like; aromatic hydrocarbons such as benzene,toluene, ethylbenzene, xylene, mesitylene and the like; ethers such asdiethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, ethyleneglycol dimethyl ether, methyl-t-butyl ether and the like; acid amidessuch as N,N-dimethylformamide, N,N-dimethylacetamide and the like;tertiary amines such as pyridine, N,N-dimethylaniline,N,N-diethylaniline, triethylamine, diisopropylethylamine and the like;sulfur compounds such as dimethyl sulfoxide, sulfolane and the like; ormixtures thereof and the like.

[0325] After completion of the reaction, an intended material can beobtained by a usual post-treatment operation such as by filtrating thereaction solution before concentrating the solution itself, or, addingan acid to the reaction solution and collecting the produced crystals byfiltration, or, adding an acid to the reaction solution, then,subjecting the mixture to extraction with an organic solvent,concentration and the like. As the acid to be added, there are listedhydrochloric acid, acetic acid, trifluoroacetic acid, p-toluenesulfonicacid, or aqueous solutions thereof and the like. This compound can alsobe purified by an operation such as re-crystallization, chromatographyand the like.

[0326] The resulted compound [XXXIX] can also be reacted with thecompound [XXXX] according to the method described in (Production Method6) without conducting post-treatment such as isolation and the like, toproduce the present compound.

[0327] (Intermediate Production Method 8)

[0328] Of compounds [III], the compound wherein Y and W are oxygen orsulfur can also be produced by a method described in the followingscheme.

[0329] Wherein, R¹, R², R¹⁵, R¹⁶, R¹⁷, X², X³ and X⁴ are the same asdefined above, R²⁰ represents C₁ to C₆ alkyl which may be substitutedsuch as methyl, ethyl, trifluoromethyl, trichloromethyl and the like,R²⁶ represents C₁ to C₆ alkyl which may be substituted such as methyl,ethyl and the like, phenyl which may be substituted such as phenyl andthe like, or phenyl C₁ to C₆ alkyl which may be substituted such asbenzyl and the like, and X¹³ represents nitro, fluorine, chlorine,bromine or iodine.

[0330] <Process A8-1>: A Process for Producing the Compound [a-2] fromthe Compound [a-1]

[0331] The compound [a-2] can be produced, for example, by de-protectingthe compound [a-1] according to a method described in “Yuki KagakuJikken no Tebiki (published by Manual of Organic Chemical Experiment)”,vol. 4, (published by Kagaku Dojin sha), Protective Groups in OrganicSynthesis (A Wiley-Interscience publication), or according to thefollowing method.

[0332] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is usually from 0 to 200° C.,and the reaction time is usually from an instant to 24 hours. Regardingthe amounts of reagents to be used in the reaction, it is theoreticalthat the amount of the reagent is 1 mol based on 1 mol of the compound[a-1], and the amounts thereof can be changed optionally depending onthe reaction condition. As the reagent used, boron trifluoride diethyletherate, boron trifluoride methanol complex, triethyloxoniumtetrafluoroborate and the like are listed. As the solvent used, there are listedaliphatic hydrocarbons such as hexane, heptane, octane, ligroin and thelike; aromatic hydrocarbons such as benzene, toluene, ethylbenzene,xylene, mesitylene and the like; aliphatic halogenated hydrocarbons suchas methylene chloride, chloroform, carbon tetrachloride,1,2-dichloroethane, 1,2,3-trichloropropane and the like, aromatichalogenated hydrocarbons such as chlorobenzene, dichlorobenzene,benzotrifluoride and the like; ethers such as 1,4-dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, methyl-t-butyl etherand the like; alcohols such as methanol, ethanol and the like, ormixtures thereof and the like.

[0333] After completion of the reaction, an intended material can beobtained by a post-treatment operation such as by pouring the reactionsolution into water, collecting the deposited crystals by filtration anddrying them, or, extracting with an organic solvent and drying andconcentrating the organic layer, or, concentrating the reaction solutionitself, and the like. This compound can also be purified by an operationsuch as re-crystallization, chromatography and the like.

[0334] <Process A8-2>: A Process for Producing the Compound [a-3]fromthe Compound [a-2]

[0335] The compound [a-3] can be produced by reacting the compound [a-2]with a compound [b-1 of the formula [b-1]

[0336] wherein, R²⁶ and X¹² are the same as defined above, in thepresence of a base.

[0337] This reaction is usually conducted in a solvent, and also can beconducted in the absence of a solvent. The reaction temperature isusually from −20 to 200° C. The reaction time is usually from an instantto 48 hours.

[0338] The amount of the compound [b-1] used in the reaction is from 0.5mol to excess, preferably from 1.0 to 1.2 mol based on 1 mol of thecompound [a-2].

[0339] The amount of the base used in the reaction is from 0.5 mol toexcess, preferably from 1.0 to 1.2 mol based on 1 mol of the compound[a-2].

[0340] The base includes inorganic bases such as sodium carbonate,sodium hydroxide and the like, organic bases such as pyridine,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, diisopropylethylamine and the like.

[0341] The solvent include aliphatic halogenated hydrocarbons such aschloroform and the like, ethers such as tetrahydrofuran, 1,4-dioxane andthe like, nitrites such as acetonitrile and the like, esters such asethyl acetate, water or mixtures thereof, and the like.

[0342] After completion of the reaction, an intended material can beobtained by a usual post-treatment operation such as by filtrating thereaction solution before concentrating the solution itself, or, pouringthe reaction solution into water and collecting the produced crystals byfiltration, or, pouring the reaction solution into water and subjectingthe mixture to extraction with an organic solvent, concentration and thelike. This compound can also be purified by an operation such asre-crystallization, chromatography and the like.

[0343] <Process A8-3>: A Process for Producing the Compound [a-5] fromthe Compound [a-3]

[0344] The compound [a-5] can be produced by reacting the compound [a-31with the compound [XXXV] in the presence of a base.

[0345] This reaction is usually conducted in a solvent, and the reactiontemperature is usually from −20 to 200° C., preferably from 0 to 130° C.The reaction time is usually from an instant to 72 hours.

[0346] The amount of the compound [XXXV] used in the reaction is from0.5 mol to excess, preferably from 0.8 to 1.2 mol based on 1 mol of thecompound [a-3].

[0347] The amount of the base used in the reaction is from 0.5 mol toexcess, preferably from 0.8 to 1.2 mol based on the compound [a-3].

[0348] The base includes organic bases such as 4-dimethylaminopyridine,diisopropylethylamine and the like, inorganic bases such as sodiumcarbonate, potassium carbonate, sodium hydride, potassium hydride andthe like, metal alkoxides such as sodium methoxide, sodium ethoxide,potassium t-butoxide and the like.

[0349] The solvent includes ketones such as acetone, methyl isobutylketone and the like; aliphatic hydrocarbons such as hexane, heptane,petroleum ether and the like; aromatic hydrocarbons such as benzene,toluene, ethylbenzene, xylene, mesitylene and the like; ethers such asdiethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, ethyleneglycol dimethyl ether, methyl-t-butyl ether and the like; nitrocompounds such as nitromethane, nitrobenzene and the like; acid amidessuch as N,N-dimethylformamide, N,N-dimethylacetamide and the like;tertiary amines such as pyridine, N,N-dimethylaniline,N,N-diethylaniline, triethylamine, diisopropylethylamine and the like;sulfur compounds such as dimethyl sulfoxide, sulfolane and the like; ormixtures thereof and the like.

[0350] After completion of the reaction, an intended material can beobtained by a post-treatment operation such as by filtrating thereaction solution before concentrating the solution itself, or, addingan acid to the reaction solution and collecting the produced crystals byfiltration, or, adding an acid to the reaction solution, then,subjecting the mixture to extraction with an organic solvent,concentration and the like. As the acid to be added, there are listedhydrochloric acid, acetic acid, trifluoroacetic acid, p-toluenesulfonicacid, or aqueous solutions thereof and the like. This compound can alsobe purified by an operation such as chromatography, re-crystallizationand the like. Further, the compound [a-5] can also be used in a reactionof the following process without isolation.

[0351] <Process A8-4>: A Process for Producing the Compound [a-4] fromthe Compound [a-2]

[0352] The compound [a-4] can be produced by isocyanating the compound[a-2] by reaction with an isocyanating agent in a solvent or in theabsence of a solvent.

[0353] Isocyanating agent: phosgene, trichloromethyl chloroformate,oxalyl chloride and the like

[0354] Amount of isocyanating agent: from 1 mol to excess based on 1 molof the compound [a-2]

[0355] Solvent: aromatic hydrocarbons such as benzene, toluene and thelike, halogenated aromatic hydrocarbons such as chlorobenzene and thelike, esters such as ethyl acetate and the like

[0356] Reaction Temperature: from room temperature to reflux temperature

[0357] Reaction Time: from an instant to 48 hours

[0358] After completion of the reaction, an intended material can beobtained by concentrating the reaction solution itself, and the like.This compound can also be purified by an operation such asre-crystallization and the like.

[0359] <Process A8-5>: A Process for Producing the Compound [a-5] fromthe Compound [a-4]

[0360] The compound [a-5] can be produced by reacting the compound [a-4]with the compound [XXXV] in a solvent in the presence of a base.

[0361] Amount of the compound [XXXV]: 0.9 to 10 mol based on 1 mol ofthe compound [a-4]

[0362] Base: inorganic bases such as sodium hydride, potassiumhydroxide, sodium hydroxide and the like, metal alkoxides such as sodiummethoxides, sodium ethoxides and the like

[0363] Amount of a base: 0.1 to 10 mol based on 1 mol of the compound[a-4]

[0364] Solvent: aromatic hydrocarbons such as benzene, toluene and thelike; halogenated aromatic hydrocarbons such as chlorobenzene and thelike; amides such as N,N-dimethylformamide and the like; ethers such astetrahydrofuran and the like; halogenated aliphatic hydrocarbons such aschloroform and the like; sulfur compounds such as dimethyl sulfoxide andthe like; and mixtures thereof

[0365] Reaction temperature: −40° C. to solvent reflux temperature

[0366] Reaction time: instant to 72 hours

[0367] After completion of the reaction, an intended material can beobtained by a post-treatment operation such as by neutralizing, then,pouring a reaction solution into water, and collecting the depositedcrystals and drying them, or, extracting with an organic solvent anddrying and concentrating the organic layer, or, concentrating a reactionsolution itself, and the like. This compound can also be purified by anoperation such as re-crystallization, chromatography and the like.

[0368] The resulted compound [a-5] can also be used in a reaction of thefollowing process without isolation.

[0369] <Process A8-6>: A Process for Producing the Compound [a-6] fromthe Compound [a-5]

[0370] The compound [a-6] can be produced by reacting the compound [a-5]with the compound [XXXX] in the presence of a base.

[0371] This reaction is usually conducted in a solvent, and the reactiontemperature is usually from −20 to 200° C., preferably from 0 to 100° C.The reaction time is usually from an instant to 48 hours.

[0372] The amount of the compound [XXXX] used in the reaction is from0.5 mol to excess, preferably from 0.8 to 1.2 mol based on 1 mol of thecompound [a-5].

[0373] The amount of the base used in the reaction is from 0.5 mol toexcess, preferably from 0.8 to 1.2 mol based on 1 mol of the compound[a-5].

[0374] The base includes organic bases such as pyridine,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, diisopropylethylamine and the like, sodium carbonate,potassium carbonate, sodium hydride, potassium hydride and the like.

[0375] The solvent include aliphatic hydrocarbons such as hexane,heptane, octane, ligroin, cyclohexane and the like; aromatichydrocarbons such as benzene, toluene, ethylbenzene, xylene, mesityleneand the like; ethers such as diethyl ether, diisopropyl ether,1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether,methyl-t-butyl ether and the like; nitro compounds such as nitromethane,nitrobenzene and the like; acid amides such as N,N-dimethylformamide,N,N-dimethylacetamide and the like; tertiary amines such as pyridine,N,N-dimethylaniline, N,N-diethylaniline, triethylamine,diisopropylethylamine and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like; alcohols such as methanol, ethanol,ethylene glycol, isopropanol, t-butnol and the like; or mixtures thereofand the like.

[0376] After completion of the reaction, an intended material can beobtained by a usual post-treatment operation such as by filtrating areaction solution before concentrating the solution itself, or, pouringa reaction solution into water and collecting the produced crystals, or,pouring a reaction solution into water, then, subjecting the mixture toextraction with an organic solvent, concentration and the like.

[0377] This compound can also be purified by an operation such aschromatography, re-crystallization and the like.

[0378] <Process A8-7>: A Process for Producing the Compound [a-7] fromthe Compound [a-6].

[0379] The compound [a-7] can be produced according to the Process A1-5of the Intermediate Production Method 1 from the compound [a-6].

[0380] (Intermediate Production Method 9)

[0381] The compound [a-1] can be produced by a method described in thefollowing scheme. (In the scheme, the compound [a-1] is represented ascompound [a-9] or compound [a-11].)

[0382] Wherein, R⁷, R¹⁵, R¹⁶, R¹⁷, R²⁰, X², X³, X⁴ and X¹² are the sameas defined above.

[0383] <Process A9-1>: A Process for Producing the Compound [a-9] fromthe Compound [a-8]

[0384] The compound [a-9] can be produced by reacting the compound [a-8]with the compound [XV] in the presence of a base.

[0385] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is usually from 0 to 200° C.,and the reaction time is usually from an instant to 24 hours.

[0386] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the compound [XV] is 1 mol and theamount of the base is 1 mol based on 1 mol of the compound [a-8], andthe amounts thereof can be changed optionally depending on the reactioncondition.

[0387] The base to be used includes organic bases such as pyridine,quinoline, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-en,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine,diisopropylethylamine and the like, metal alkoxides such as sodiummethoxide, sodium ethoxide, potassium t-butoxide and the like, andinorganic bases such as lithium carbonate, sodium carbonate, potassiumcarbonate, calcium carbonate, barium carbonate, sodium hydrogencarbonate, potassium hydrogen carbonate, sodium hydride, potassiumhydride, lithium hydroxide, sodium hydroxide, potassium hydroxide,calcium hydroxide, barium hydroxide and the like.

[0388] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether andthe like; aromatic hydrocarbons such as benzene, toluene, xylene and thelike; aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;ketones such as acetone, 2-butanone, methyl isobutyl ketone and thelike; esters such as ethyl formate, ethyl acetate, butyl acetate,diethyl carbonate and the like; nitro compounds such as nitromethane,nitrobenzene and the like; nitriles such as acetonitrile,isobutyronitrile and the like; acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfurcompounds such as dimethyl sulfoxide, sulfolane and the like; alcoholssuch as methanol, ethanol, ethylene glycol, isopropanol, t-butanol andthe like; or mixtures thereof.

[0389] After completion of the reaction, an intended material can beobtained, for example, by the following operation 1) or 2).

[0390] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0391] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0392] Further, the intended material can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0393] <Process A9-2>: A Process for Producing the Compound [a-10] fromthe Compound [a-9]

[0394] The compound [a-10] can be produced, for example, by reducing thecompound [a-9] using an iron powder in the presence of an acid in asolvent.

[0395] The reaction temperature of this reaction is usually from 0 to200° C., preferably from room temperature to the reflux temperature. Thereaction time is usually from an instant to 24 hours.

[0396] Regarding the amounts of reagents to be used in the reaction, theamount of the iron powder is from 3 mol to excess and the amount of theacid is 1 to 10 mol based on 1 mol of the compound [a-9], and theamounts thereof can be changed optionally depending on the reactioncondition.

[0397] As the acid to be used, acetic acid and the like are listed.

[0398] As the solvent to be used, there are listed, for example, water,acetic acid, ethyl acetate and the like or mixtures thereof.

[0399] After completion of the reaction, an intended material can beobtained by a usual post-treatment such as by pouring a reactionsolution into water directly or after filtration and collecting theproduced crystals, or, extracting with an organic solvent,neutralization, concentration and the like.

[0400] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0401] <Process A9-3>: A Process for Producing the Compound [a-11] fromthe Compound [a-10].

[0402] The compound [a-11] can be produced by i) diazotizing thecompound [a-10] in a solvent, then, ii) subsequently, reacting the diazocompound with potassium iodide, copper (I) bromide, copper (I) chlorideor hydroborofluoric acid in a solvent.

[0403] In the diazotization reaction of the first step, the reactiontemperature is from −20 to 20° C., and the reaction time is usually froman instant to 5 hours.

[0404] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the diazotization agent is 1 mol basedon 1 mol of the compound [a-10], and the amounts thereof can be changedoptionally depending on the reaction condition.

[0405] As the diazotization agent to be used, nitrites such as sodiumnitrite, potassium nitrite, isoamyl nitrite, t-butyl nitrite and thelike, are listed.

[0406] As the solvent, there are listed, for example, acetonitrile,hydrobromic acid, hydrochloric acid, sulfuric acid, water and the likeor mixtures thereof.

[0407] The reaction solution after completion of the reaction is used asit is in the following reaction.

[0408] In the reaction of the second step, the reaction temperature isfrom 0 to 80° C., and the reaction time is usually from an instant to 24hours.

[0409] Regarding the amounts of reagents to be used in the reaction,each amount of potassium iodide, copper (I) bromide, copper (I) chlorideor hydroborofluoric acid is from 1 to 3 mol based on 1 mol of thecompound [a-10], and the amounts thereof can be changed optionallydepending on the reaction condition. When copper [I] bromide is used,the reaction can also be conducted in the presence of copper (II)bromide, and when copper (I) chloride is used, the reaction can also beconducted in the presence of copper (II) chloride.

[0410] As the solvent to be used, there are listed, for example,acetonitrile, diethyl ether, t-butyl methyl ether, hydrobromic acid,hydrochloric acid, sulfuric acid, water and the like or mixturesthereof.

[0411] After completion of the reaction, an intended material can beobtained by collecting the produced crystals by filtration (ifnecessary, by adding water), or, extracting with an organic solvent,concentration and the like.

[0412] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0413] Further, this reaction is not limited to the above-mentionedmethods, and production can also be conducted by reacting the compound[a-10] with the diazotizing agent in a solvent (for example,acetonitrile, diethyl ether, t-butyl methyl ether, hydrobromic acid,hydrochloric acid, sulfuric acid, water or mixtures thereof) in thepresence of potassium iodide, copper (I) bromide, copper (I) chloride orhydroborofluoric acid.

[0414] (Intermediate Production Method 10)

[0415] The compound [III] wherein X¹ is nitro, fluorine, chlorine,bromine or iodine, and Y and W are oxygen or sulfur can also be producedby a method described in the following scheme.

[0416] Wherein, R¹, R², R⁷, R¹⁷, X², X³, X⁴ and X¹² are the same asdefined above.

[0417] <Process A10-1>: A Process for Producing the Compound [a-12] fromthe Compound [XIV]

[0418] The compound [a-12] can be produced by reacting the compound[XIV] with the compound [b-2] of the formula [b-2]

[0419] wherein, R¹⁷, X³ and X⁴ are the same as defined above,

[0420] in the presence of a base.

[0421] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is usually from 0 to 200° C.,and the reaction time is usually from an instant to 24 hours.

[0422] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the compound [b-2] is 1 mol and theamount of the base is 1 mol based on 1 mol of the compound [XIV], andthe amounts thereof can be changed optionally depending on the reactioncondition.

[0423] The base to be used includes organic bases such as pyridine,quinoline, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-en,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine,diisopropylethylamine and the like, and inorganic bases such as lithiumcarbonate, sodium carbonate, potassium carbonate, calcium carbonate,barium carbonate and the like.

[0424] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether andthe like; aromatic hydrocarbons such as benzene, toluene, xylene and thelike; aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;ketones such as acetone, 2-butanone, methyl isobutyl ketone and thelike; esters such as ethyl formate, ethyl acetate, butyl acetate,diethyl carbonate and the like; nitro compounds such as nitromethane,nitrobenzene and the like; nitriles such as acetonitrile,isobutyronitrile and the like; acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfurcompounds such as sulfolane and the like; or mixtures thereof.

[0425] After completion of the reaction, an intended material can beobtained, for example, by the following operation 1) or 2).

[0426] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0427] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0428] Further, the intended material can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0429] <Process A10-2>: A Process for Producing the Compound [a-13] fromthe Compound [a-12]

[0430] The compound [a-13] can be produced, for example, by reducing thecompound [a-12] using an iron powder in the presence of an acid in asolvent.

[0431] The reaction temperature of this reaction is usually from 0 to200° C., preferably from room temperature to the reflux temperature. Thereaction time is usually from an instant to 24 hours.

[0432] Regarding the amounts of reagents to be used in the reaction, theamount of the iron powder is from 3 mol to excess and the amount of theacid is 1 to 10 mol based on 1 mol of the compound [a-12], and theamounts thereof can be changed optionally depending on the reactioncondition.

[0433] As the acid to be used, acetic acid and the like are listed.

[0434] As the solvent to be used, there are listed, for example, water,acetic acid, ethyl acetate and the like or mixtures thereof.

[0435] After completion of the reaction, an intended material can beobtained by pouring a reaction solution into water directly or afterfiltration and collecting the produced crystals by filtration, or,extracting with an organic solvent, neutralization, concentration andthe like.

[0436] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0437] <Process A10-3>: A Process for Producing the Compound [a-14] fromthe Compound [a-13].

[0438] The compound [a-14] can be produced by i) diazotizing thecompound [a-13] in a solvent, then, ii) subsequently, reacting the diazocompound with potassium iodide, copper (I) bromide, copper (I) chlorideor hydroborofluoric acid in a solvent.

[0439] In the diazotization reaction of the first step, the reactiontemperature is from −20 to 20° C., and the reaction time is usually froman instant to 5 hours.

[0440] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the diazotization agent is 1 mol basedon 1 mol of the compound [a-13], and the amounts thereof can be changedoptionally depending on the reaction condition.

[0441] As the diazotization agent to be used, nitrites such as sodiumnitrite, potassium nitrite and the like, organic nitrous acid compoundssuch as isoamyl nitrite, t-butyl nitrite and the like, are listed.

[0442] As the solvent, there are listed, for example, acetonitrile,hydrobromic acid, hydrochloric acid, sulfuric acid, water and the likeor mixtures thereof.

[0443] The reaction solution after completion of the reaction is used asit is in the following reaction.

[0444] In the reaction of the second step, the reaction temperature isfrom 0 to 80° C., and the reaction time is usually from an instant to 24hours.

[0445] Regarding the amounts of reagents to be used in the reaction,each amount of potassium iodide, copper (I) bromide, copper (I) chlorideor hydroborofluoric acid is from 1 to 3 mol based on 1 mol of thecompound [a-13], and the amounts thereof can be changed optionallydepending on the reaction condition. When copper (I) bromide is used,the reaction can also be conducted in the presence of copper (II)bromide, and when copper (I) chloride is used, the reaction can also beconducted in the presence of copper (II) chloride.

[0446] As the solvent to be used, there are listed, for example,acetonitrile, diethyl ether, t-butyl methyl ether, hydrobromic acid,hydrochloric acid, sulfuric acid, water and the like or mixturesthereof.

[0447] After completion of the reaction, an intended material can beobtained by collecting the produced crystals (if necessary, by addingwater), or, extracting with an organic solvent, concentration and thelike.

[0448] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0449] Further, this reaction is not limited to the above-mentionedmethods, and production can also be conducted by reacting the compound[a-13] with the diazotizing agent in a solvent (for example,acetonitrile, diethyl ether, t-butyl methyl ether, hydrobromic acid,hydrochloric acid, sulfuric acid, water or mixtures thereof) in thepresence of potassium iodide, copper (I) bromide, copper (I) chloride orhydroborofluoric acid.

[0450] (Intermediate Production Method 11)

[0451] Of the compounds [III], the compound wherein Y and W are oxygencan also be produced by a method described in the following scheme.

[0452] Wherein, R¹, R², R²⁰, X¹, X², X³ and X⁴ are the same as definedabove.

[0453] <Process A11-1>: A Process for Producing the Compound [a-16] fromthe Compound [a-15]

[0454] The compound [a-16] can be produced, for example, byde-protecting the compound [a-15] according to a method described in“Yuki Kagaku Jikken no Tebiki (published by Manual of Organic ChemicalExperiment)”, vol. 4, (published by Kagaku Dojin sha), Protective Groupsin Organic Synthesis (published by A Wiley-Interscience publication), oraccording to the following method.

[0455] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is usually from 0 to 200° C.,and the reaction time is usually from an instant to 24 hours. Regardingthe amounts of reagents to be used in the reaction, it is theoreticalthat the amount of the reagent is 1 mol based on 1 mol of the compound[a-15], and the amounts thereof can be changed optionally depending onthe reaction condition. As the reagent used, boron trifluoride methanolcomplex, triethyloxoniumtetrafluoro borate and the like are listed. Asthe solvent used, there are listed aliphatic hydrocarbons such ashexane, heptane, octane, ligroin and the like; aromatic hydrocarbonssuch as benzene, toluene, ethylbenzene, xylene, mesitylene and the like;aliphatic halogenated hydrocarbons such as methylene chloride,chloroform, carbon tetrachloride, 1,2-dichloroethane,1,2,3-trichloropropane and the like, aromatic halogenated hydrocarbonssuch as chlorobenzene, dichlorobenzene, benzotrifluoride and the like;ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethylether, methyl-t-butyl ether and the like; alcohols such as methanol,ethanol and the like, or mixtures thereof and the like.

[0456] After completion of the reaction, an intended material can beobtained by a post-treatment operation such as by pouring a reactionsolution into water and collecting the deposited crystals and dryingthem, or, extracting with an organic solvent and drying andconcentrating the organic layer, or, concentrating a reaction solutionitself, and the like. This compound can also be purified by an operationsuch as re-crystallization, chromatography and the like.

[0457] <Process A11-2>: A Process for Producing the Compound [a-17] fromthe Compound [a-16]

[0458] The compound [a-17] can be produced by isocyanating the compound[a-16] by reaction with an isocyanating agent in a solvent or in theabsence of a solvent.

[0459] Isocyanating agent: phosgene, trichloromethyl chloroformate,oxalyl chloride and the like

[0460] Amount of isocyanating agent: from 1 mol to excess based on 1 molof the compound [a-16]

[0461] Solvent: aromatic hydrocarbons such as benzene, toluene and thelike, halogenated aromatic hydrocarbons such as chlorobenzene and thelike, esters such as ethyl acetate and the like

[0462] Reaction Temperature: from room temperature to reflux temperature

[0463] Reaction Time: from an instant to 48 hours

[0464] After completion of the reaction, an intended material can beobtained by concentrating a reaction solution itself, and the like. Thiscompound can also be purified by an operation such as re-crystallizationand the like.

[0465] <Process A11-3>: A Process for Producing the Compound [a-18] fromthe Compound [a-17]

[0466] The compound [a-18] can be produced by reacting the compound[a-17] with the compound [XXXV] in a solvent in the presence of a base.

[0467] Amount of the compound [XXXV]: 0.9 to 10 mol based on 1 mol ofthe compound [a-17]

[0468] Base: inorganic bases such as sodium hydride, potassium hydride,sodium hydroxide and the like, metal alkoxides such as sodium methoxide,sodium ethoxide and the like

[0469] Amount of a base: 0.1 to 10 mol based on 1 mol of the compound[a-17]

[0470] Solvent: aromatic hydrocarbons such as benzene, toluene and thelike; halogenated aromatic hydrocarbons such as chlorobenzene and thelike; amides such as N,N-dimethylformamide and the like; ethers such astetrahydrofuran and the like; halogenated aliphatic hydrocarbons such aschloroform and the like; and mixtures thereof

[0471] Reaction temperature: −40° C. to solvent reflux temperature

[0472] Reaction time: instant to 72 hours

[0473] After completion of the reaction, an intended material can beobtained by a post-treatment operation such as by neutralizing, then,pouring a reaction solution into water, and collecting the depositedcrystals by filtration, or, extracting with an organic solvent anddrying and concentrating the organic layer, or, concentrating a reactionsolution itself, and the like. This compound can also be purified by anoperation such as re-crystallization, chromatography and the like.

[0474] The compound [a-18] can also be used in the reaction of thefollowing process without isolation.

[0475] <Process A11-4>: A Process for Producing the Compound [a-29] fromthe Compound [a-18]

[0476] The compound [a-29] can be produced by reacting the compound[a-18] with the compound [XXXX] in the presence of a base.

[0477] This reaction is usually conducted in a solvent, and the reactiontemperature is usually from −20 to 200° C., preferably from 0 to 100° C.The reaction time is usually from an instant to 48 hours.

[0478] The amount of the compound [XXXX] used in the reaction is from0.5 mol to excess, preferably from 0.8 to 1.2 mol based on 1 mol of thecompound [a-18].

[0479] The amount of the base used in the reaction is from 0.5 mol toexcess, preferably from 0.8 to 1.2 mol based on 1 mol of the compound[a-18].

[0480] The base includes organic bases such as pyridine,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, diisopropylethylamine and the like, sodium carbonate,potassium carbonate, sodium hydride, potassium hydride and the like.

[0481] The solvent include aliphatic hydrocarbons such as hexane,heptane, octane, ligroin, cyclohexane, petroleum ether and the like;aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene,mesitylene and the like; ethers such as diethyl ether, diisopropylether, 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether,methyl-t-butyl ether and the like; nitro compounds such as nitromethane,nitrobenzene and the like; acid amides such as N,N-dimethylformamide,N,N-dimethylacetamide and the like; tertiary amines such as pyridine,N,N-dimethylaniline, N,N-diethylaniline, triethylamine,diisopropylethylamine and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like; or mixtures thereof and the like.

[0482] After completion of the reaction, an intended material can beobtained by a usual post-treatment operation such as by filtrating areaction solution before concentrating the solution itself, or, pouringa reaction solution into water and collecting the produced crystals, or,pouring a reaction solution into water, then, subjecting the mixture toextraction with an organic solvent, concentration and the like. Thiscompound can also be purified by an operation such as chromatography,re-crystallization and the like.

[0483] (Intermediate Production Method 12)

[0484] The compound [XXXII] wherein X¹ is nitro, fluorine, chlorine,bromine or iodine can also be produced by a method described in thefollowing scheme.

[0485] Wherein, R⁴, R⁵, R⁷, R¹⁷, R²⁰, W, X², X¹, X⁴, X¹² and X¹³ are thesame as defined above.

[0486] <Process A12-1>: A Process for Producing the Compound [a-20] fromthe Compound [a-19]

[0487] The compound [a-20] can be produced by reacting the compound[a-19] with a compound [b-3] of the formula [b-3]

[0488] wherein, R⁴, R⁵, R¹⁷, W, Y, X³, and X⁴ are the same as definedabove,

[0489] in the presence of a base.

[0490] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is usually from 0 to 200° C.,and the reaction time is usually from an instant to 24 hours.

[0491] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the compound [b-3] is 1 mol and theamount of the base is 1 mol based on 1 mol of the compound [a-19], andthe amounts thereof can be changed optionally depending on the reactioncondition.

[0492] The base to be used includes organic bases such as pyridine,quinoline, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-en,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine,diisopropylethylamine and the like, and inorganic bases such as lithiumcarbonate, sodium carbonate, potassium carbonate, calcium carbonate,barium carbonate, sodium hydrogen carbonate, potassium hydrogencarbonate, sodium hydride, potassium hydride and the like.

[0493] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether andthe like; aromatic hydrocarbons such as benzene, toluene, xylene and thelike; aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;ketones such as acetone, 2-butanone, methyl isobutyl ketone and thelike; esters such as ethyl formate, ethyl acetate, butyl acetate,diethyl carbonate and the like; nitro compounds such as nitromethane,nitrobenzene and the like; nitriles such as acetonitrile,isobutyronitrile and the like; acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfurcompounds such as dimethyl sulfoxide, sulfolane and the like; ormixtures thereof.

[0494] After completion of the reaction, an intended material can beobtained, for example, by the following operation 1) or 2).

[0495] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0496] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0497] Further, the intended material can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0498] <Process A12-2>: A Process for Producing the Compound [a-21] fromthe Compound [a-20]

[0499] The compound [a-21] can be produced, for example, by reducing thecompound [a-20] using an iron powder in the presence of an acid in asolvent.

[0500] The reaction temperature of this reaction is usually from 0 to200° C., preferably from room temperature to the reflux temperature. Thereaction time is usually from an instant to 24 hours.

[0501] Regarding the amounts of reagents to be used in the reaction, theamount of the iron powder is from 3 mol to excess and the amount of theacid is 1 to 10 mol based on 1 mol of the compound [a-20], and theamounts thereof can be changed optionally depending on the reactioncondition.

[0502] As the acid to be used, acetic acid and the like are listed.

[0503] As the solvent to be used, there are listed, for example, water,acetic acid, ethyl acetate and the like or mixtures thereof.

[0504] After completion of the reaction, an intended material can beobtained by usual post-treatment such as by pouring a reaction solutioninto water directly or after filtration and collecting the producedcrystals by filtration, or, extracting with an organic solvent,neutralization, concentration and the like.

[0505] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0506] <Process A12-3>: A Process for Producing the Compound [a-22] fromthe Compound [a-21].

[0507] The compound [a-22] can be produced by i) diazotizing thecompound [a-21] in a solvent, then, ii) subsequently, reacting the diazocompound with potassium iodide, copper (I) bromide, copper (I) chlorideor hydroborofluoric acid in a solvent.

[0508] In the diazotization reaction of the first step, the reactiontemperature is from −20 to 20° C., and the reaction time is usually froman instant to 5 hours.

[0509] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the diazotization agent is 1 mol basedon 1 mol of the compound [a-21], and the amounts thereof can be changedoptionally depending on the reaction condition.

[0510] As the diazotization agent to be used, nitrites such as sodiumnitrite, potassium nitrite, isoamyl nitrite, t-butyl nitrite and thelike, are listed.

[0511] As the solvent, there are listed, for example, acetonitrile,hydrobromic acid, hydrochloric acid, sulfuric acid, water and the likeor mixtures thereof.

[0512] The reaction solution after completion of the reaction is used asit is in the following reaction.

[0513] In the reaction of the second step, the reaction temperature isfrom 0 to 80° C., and the reaction time is usually from an instant to 24hours.

[0514] Regarding the amounts of reagents to be used in the reaction,each amount of potassium iodide, copper (I) bromide, copper (I) chlorideor hydroborofluoric acid is from 1 to 3 mol based on 1 mol of thecompound [a-21], and the amounts thereof can be changed optionallydepending on the reaction condition. When copper (I) bromide is used,the reaction can also be conducted in the presence of copper (II)bromide, and when copper (I) chloride is used, the reaction can also beconducted in the presence of copper (II) chloride.

[0515] As the solvent to be used, there are listed, for example,acetonitrile, diethyl ether, t-butyl methyl ether, hydrobromic acid,hydrochloric acid, sulfuric acid, water and the like or mixturesthereof.

[0516] After completion of the reaction, an intended material can beobtained by usual post-treatment such as collecting the producedcrystals (if necessary, by adding water), or, extracting with an organicsolvent, concentration and the like.

[0517] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0518] Further, this reaction is not limited to the above-mentionedmethods, and production can also be conducted by reacting the compound[a-21] with the diazotizing agent in a solvent (for example,acetonitrile, diethyl ether, t-butyl methyl ether, hydrobromic acid,hydrochloric acid, sulfuric acid, water or mixtures thereof) in thepresence of potassium iodide, copper (I) bromide, copper (I) chloride orhydroborofluoric acid.

[0519] When copper (I) bromide is used, the reaction can also beconducted in the presence of copper (II) bromide, and when copper (I)chloride is used, the reaction can also be conducted in the presence ofcopper (II) chloride.

[0520] <Process A12-4>: A Process for Producing the Compound [a-23] fromthe Compound [a-22]

[0521] The compound [a-23] can be produced, for example, byde-protecting the compound [a-22] according to a method described in“Yuki Kagaku Jikken no Tebiki (published by Manual of Organic ChemicalExperiment)”, vol. 4, (published by Kagaku Dojin sha), Protective Groupsin Organic Synthesis (published by A Wiley-Interscience publication), oraccording to the following method.

[0522] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is usually from 0 to 200° C.,and the reaction time is usually from an instant to 24 hours. Regardingthe amounts of reagents to be used in the reaction, it is theoreticalthat the amount of the reagent is 1 mol based on 1 mol of the compound[a-22], and the amounts thereof can be changed optionally depending onthe reaction condition. As the reagent used, boron trifluoride methanolcomplex, triethyloxoniumtetrafluoro borate and the like are listed. Asthe solvent used, there are listed aliphatic hydrocarbons such ashexane, heptane, octane, ligroin and the like; aromatic hydrocarbonssuch as benzene, toluene, ethylbenzene, xylene, mesitylene and the like;aliphatic halogenated hydrocarbons such as methylene chloride,chloroform, carbon tetrachloride, 1,2-dichloroethane,1,2,3-trichloropropane and the like, aromatic halogenated hydrocarbonssuch as chlorobenzene, dichlorobenzene, benzotrifluoride and the like;ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethylether, methyl-t-butyl ether and the like; alcohols such as methanol,ethanol and the like, or mixtures thereof and the like.

[0523] After completion of the reaction, an intended material can beobtained by a post-treatment operation such as by pouring a reactionsolution into water and collecting the deposited crystals by filtrationand drying them, or, extracting with an organic solvent and drying andconcentrating the organic layer, or, concentrating a reaction solutionitself, and the like. This compound can also be purified by an operationsuch as re-crystallization, chromatography and the like.

[0524] <Process A12-5>: A Process for Producing the Compound [a-23] fromthe Compound [a-20]

[0525] The compound [a-23] wherein X¹³ is nitro can be producedaccording to the method described in <Process A12-4> from the compound[a-20].

[0526] (Intermediate Production Method 13)

[0527] The compound [XXXIV] and the compound [a-15] wherein X¹ is nitro,fluorine, chlorine, bromine or iodine, the compound [a-20], and thecompound [a-22] can also be produced by methods described in thefollowing scheme.

[0528] Wherein, R⁴, R⁵, R⁷, R¹⁷, X², X³, X⁴, X¹² and X¹³ are the same asdefined above, R²⁵ represents C₁ to C₆ alkyl which may be substitutedsuch as methyl, ethyl, trifluoromethyl, trichloromethyl and the like: orC₁ to C₆ alkoxy which may be substituted such as methoxy, ethoxy and thelike: or phenoxy which may be substituted such as phenoxy and the like.

[0529] <Process A13-1>: A Process for Producing the Compound [a-25] fromthe Compound [a-24]

[0530] The compound [a-25] can be produced by reacting the compound[a-24] with the compound [b-21 in the presence of a base.

[0531] This reaction is conducted usually in the absence of a solvent orin a solvent, and the reaction temperature is usually from 0 to 200° C.,and the reaction time is usually from an instant to 24 hours.

[0532] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the compound [b-2] is 1 mol and theamount of the base is 1 mol based on 1 mol of the compound [a-24], andthe amounts thereof can be changed optionally depending on the reactioncondition.

[0533] The base to be used includes organic bases such as pyridine,quinoline, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-en,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine,diisopropylethylamine and the like, and inorganic bases such as lithiumcarbonate, sodium carbonate, potassium carbonate, calcium carbonate,barium carbonate, sodium hydrogen carbonate, potassium hydrogencarbonate, sodium hydride, potassium hydride, lithium hydroxide, sodiumhydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide andthe like.

[0534] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether andthe like; aromatic hydrocarbons such as benzene, toluene, xylene and thelike; aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;ketones such as acetone, 2-butanone, methyl isobutyl ketone and thelike; esters such as ethyl formate, ethyl acetate, butyl acetate,diethyl carbonate and the like; nitro compounds such as nitromethane,nitrobenzene and the like; nitriles such as acetonitrile,isobutyronitrile and the like; acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfurcompounds such as dimethyl sulfoxide, sulfolane and the like; ormixtures thereof.

[0535] This reaction may sometimes be accelerated by using a catalyst.As the catalyst, copper iodide, copper bromide, copper chloride, copperpowder and the like are listed, and the amount of the catalyst used inthe reaction is from 0.0001 to 0.1 mol based on 1 mol of the compound[a-24], and the amounts thereof can be changed optionally depending onthe reaction condition.

[0536] After completion of the reaction, an intended material can beobtained, for example, by the following operation 1) or 2).

[0537] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0538] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0539] Further, the intended material can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0540] <Process A13-2>: A Process for Producing the Compound [a-26] fromthe Compound [a-25]

[0541] The compound [a-26] can be produced, for example, by reducing thecompound [a-25] using an iron powder in the presence of an acid in asolvent.

[0542] The reaction temperature of this reaction is usually from 0 to200° C., preferably from room temperature to the reflux temperature. Thereaction time is usually from an instant to 24 hours.

[0543] Regarding the amounts of reagents to be used in the reaction, theamount of the iron powder is from 3 mol to excess and the amount of theacid is 1 to 10 mol based on 1 mol of the compound [a-25], and theamounts thereof can be changed optionally depending on the reactioncondition.

[0544] As the acid to be used, acetic acid and the like are listed.

[0545] As the solvent to be used, there are listed, for example, water,acetic acid, ethyl acetate and the like or mixtures thereof.

[0546] After completion of the reaction, an intended material can beobtained by usual post-treatment such as by pouring a reaction solutionin to water directly or after filtration and collecting the producedcrystals by filtration, or, extracting with an organic solvent,neutralization, drying, concentration and the like.

[0547] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0548] <Process A13-3>: A Process for Producing the Compound [a-27] fromthe Compound [a-26]

[0549] The compound [a-27] can be produced by i) diazotizing thecompound [a-26] in a solvent, then, ii) subsequently, reacting the diazocompound with potassium iodide, copper (I) bromide, copper (I) chlorideor hydroborofluoric acid in a solvent.

[0550] In the diazotization reaction of the first step, the reactiontemperature is from −20 to 20° C., and the reaction time is usually froman instant to 5 hours.

[0551] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the diazotization agent is 1 mol basedon 1 mol of the compound [a-26], and the amounts thereof can be changedoptionally depending on the reaction condition.

[0552] As the diazotization agent to be used, nitrites such as sodiumnitrite, potassium nitrite, isoamyl nitrite, t-butyl nitrite and thelike, are listed.

[0553] As the solvent, there are listed, for example, acetonitrile,hydrobromic acid, hydrochloric acid, sulfuric acid, water and the likeor mixtures thereof.

[0554] The reaction solution after completion of the reaction is used asit is in the following reaction.

[0555] In the reaction of the second step, the reaction temperature isfrom 0 to 80° C., and the reaction time is usually from an instant to 24hours.

[0556] Regarding the amounts of reagents to be used in the reaction,each amount of potassium iodide, copper (I) bromide, copper (I) chlorideor hydroborofluoric acid is from 1 to 3 mol based on 1 mol of thecompound [a-26], and the amounts thereof can be changed optionallydepending on the reaction condition. When copper [I] bromide is used,the reaction can also be conducted in the presence of copper (II)bromide, and when copper (I) chloride is used, the reaction can also beconducted in the presence of copper (II) chloride.

[0557] As the solvent to be used, there are listed, for example,acetonitrile, diethyl ether, t-butyl methyl ether, hydrobromic acid,hydrochloric acid, sulfuric acid, water and the like or mixturesthereof.

[0558] After completion of the reaction, an intended material can beobtained by usual post-treatment such as by collecting the producedcrystals by filtration (if necessary, by adding water), or, extractingwith an organic solvent, concentration and the like.

[0559] The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0560] Further, this reaction is not limited to the above-mentionedmethods, and production can also be conducted by reacting the compound[a-26] with the diazotizing agent in a solvent (for example,acetonitrile, diethyl ether, t-butyl methyl ether, hydrobromic acid,hydrochloric acid, sulfuric acid, water or mixtures thereof) in thepresence of potassium iodide, copper (I) bromide, copper (I) chloride orhydroborofluoric acid. When copper [I] bromide is used, the reaction canalso be conducted in the presence of copper (II) bromide, and whencopper (I) chloride is used, the reaction can also be conducted in thepresence of copper (II) chloride.

[0561] <Process A13-4>: A Process for Producing the Compound [a-28] fromthe Compound [a-27]

[0562] The compound [a-28] can be produced by reacting the compound[a-27] with the compound [IV] in the presence of a base.

[0563] This reaction is conducted usually in a solvent, and the reactiontemperature is usually from 0 to 200° C., and the reaction time isusually from an instant to 72 hours.

[0564] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the compound [IV] is 1 mol and theamount of the base is 1 mol based on 1 mol of the compound [a-27], andthe amounts thereof can be changed optionally depending on the reactioncondition.

[0565] The base to be used includes organic bases such as pyridine,quinoline, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-en,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine,diisopropylethylamine and the like, and inorganic bases such as lithiumcarbonate, sodium carbonate, potassium carbonate, calcium carbonate,barium carbonate, sodium hydrogen carbonate, potassium hydrogencarbonate, sodium hydride, potassium hydride and the like.

[0566] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether andthe like; aromatic hydrocarbons such as benzene, toluene, xylene and thelike; aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;ketones such as acetone, 2-butanone, methyl isobutyl ketone and thelike; esters such as ethyl formate, ethyl acetate, butyl acetate,diethyl carbonate and the like; nitriles such as acetonitrile,isobutyronitrile and the like; acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfurcompounds such as dimethyl sulfoxide, sulfolane and the like; ormixtures thereof.

[0567] After completion of the reaction, an intended material can beobtained, for example, by the following operation 1) or 2).

[0568] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0569] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0570] Further, the intended material can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0571] <Process A13-5>: A Process for Producing the Compound [a-28] fromthe Compound [a-25]

[0572] The compound [a-28] wherein X¹³ is nitro can be produced byreacting the compound [a-25] with the compound [IV] in the presence of abase.

[0573] This reaction is conducted usually in a solvent, and the reactiontemperature is usually from 0 to 200° C., and the reaction time isusually from an instant to 72 hours.

[0574] Regarding the amounts of reagents to be used in the reaction, itis theoretical that the amount of the compound [IV] is 1 mol and theamount of the base is 1 mol based on 1 mol of the compound [a-25], andthe amounts thereof can be changed optionally depending on the reactioncondition.

[0575] The base to be used includes organic bases such as pyridine,quinoline, benzyldimethylamine, phenetyldimethylamine,N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-en,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline,triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine,diisopropylethylamine and the like, and inorganic bases such as lithiumcarbonate, sodium carbonate, potassium carbonate, calcium carbonate,barium carbonate, sodium hydrogen carbonate, potassium hydrogencarbonate, sodium hydride, potassium hydride and the like.

[0576] Examples of the solvent to be used include aliphatic hydrocarbonssuch as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether andthe like; aromatic hydrocarbons such as benzene, toluene, xylene and thelike; aromatic halogenated hydrocarbons such as chlorobenzene,dichlorobenzene, benzotrifluoride and the like; ethers such as diethylether, diisopropyl ether, methyl-t-butyl ether, dioxane,tetrahydrofuran, ethylene glycol dimethyl ether, diglyme and the like;ketones such as acetone, 2-butanone, methyl isobutyl ketone and thelike; esters such as ethyl formate, ethyl acetate, butyl acetate,diethyl carbonate and the like; nitriles such as acetonitrile,isobutyronitrile and the like; acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfurcompounds such as dimethyl sulfoxide, sulfolane and the like; ormixtures thereof.

[0577] After completion of the reaction, an intended material can beobtained, for example, by the following operation 1) or 2).

[0578] 1) A reaction solution is poured into water, this is extractedwith an organic solvent, and the resulted organic layer is dried andconcentrated.

[0579] 2) A reaction solution is concentrated itself, or, filtrated ifnecessary before the filtrate is concentrated.

[0580] Further, the intended material can also be purified by aprocedure such as chromatography, re-crystallization and the like.

[0581] (Intermediate Production Method 14)

[0582] The compound [III] wherein W is oxygen can also be produced by amethod described in the following scheme.

[0583] Wherein, R¹, R², R⁶, X¹, X², X³, X⁴ and Y are the same as definedabove, R²³ represents formyl, alkylcarbonyl which may be substitutedsuch as acetyl and the like, or alkoxycarbonyl which may be substitutedsuch as methoxycarbonyl and the like, and R²⁴ represents hydrogen, alkylwhich may be substituted such as methyl and the like, or alkoxy whichmay be substituted such as methoxy.

[0584] (Intermediate Production Method 15)

[0585] The compound [III] wherein X⁴ is hydrogen, fluorine, chlorine,bromine or iodine can also be produced by a method described in thefollowing scheme.

[0586] Wherein, R¹, R², R⁶, R⁶, W, X¹, X², X³, X² and Y are the same asdefined above.

[0587] (Intermediate Production Method 16)

[0588] Compounds [a-25] and α-27] wherein R²⁵ is defined as R²⁰ can alsobe produced by a method described in the following scheme.

[0589] Wherein, R¹⁶, R¹⁷, R²⁰, X², X³, X⁴ and X¹³ are the same asdefined above.

[0590] The compound [a-42] can be produced, from the compound [a-41]according to a method described in Protective Groups in OrganicSynthesis (published by A Wiley-Interscience publication) using borontribromide, HBr/acetic acid, conc. hycrochloric acid or conc. sulfuricacid and the like.

[0591] Amount of reagent: from 1 mol to excess based on 1 mol of thecompound [a-41]

[0592] Solvent: aromatic hydrocarbons such as benzene, toluene and thelike, halogenated aliphatic hydrocarbons such as methylene chloride,chloroform and the like, halogenated aromatic hydrocarbons such aschlorobenzene and the like, or the mixture thereof.

[0593] Reaction Temperature: from −20° C. to reflux temperature

[0594] Reaction Time: from an instant to 48 hours

[0595] After completion of the reaction, an intended material can beobtained by a post-treatment operation such as by pouring a reactionsolution into water or adding an acid such as conc. hydrochloric acidand the like to a reaction solution and collecting the depositedcrystals by filtration, or, extracting a reaction solution with anorganic solvent and drying and concentrating the organic layer, or,concentrating a reaction solution itself, and the like. This compoundcan also be purified by an operation such as re-crystallization,chromatography and the like.

[0596] In the case of the compound [a-41] wherein R¹⁶ is benzyl whichmay be substituted, the compound [a-42] can also be produced from thecompound [a-41] by hydrogenation in the presence of a catalyst.

[0597] This reaction is usually conducted in a solvent, the reactiontemperature is usually from −20 to 150° C., preferably from 0 to 50° C.The reaction time is usually from an instant to 48 hours.

[0598] This reaction can also be conducted under pressure, and thereaction is preferably conducted under a pressure of 1 to 5 atom.

[0599] The amount of the catalyst used in this reaction is from 0.001 to100% by weight based on the compound [a-41].

[0600] As the catalyst to be used in the reaction, anhydrouspalladium/carbon, water-containing palladium/carbon, platinum oxide andthe like are listed.

[0601] The solvent includes carboxylic acids such as formic acid, aceticacid, propionic acid and the like, esters such as ethyl formate, ethylacetate, butyl acetate, diethyl carbonate and the like; ethers such as1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and thelike; alcohols such as methanol, ethanol, propanol, isopropanol,butanol, t-butanol, amyl alcohol, isoamyl alcohol, t-amyl alcohol andthe like; water, or mixtures thereof and the like.

[0602] After completion of the reaction, an intended material can beobtained by a usual post-treatment operation such as by filtrating areaction solution before concentrating the solution itself, and thelike. The intended material can also be purified by a procedure such aschromatography, re-crystallization and the like.

[0603] The compound [XXXXII] can be produced, for example, by a methoddescribed in WO98/08824 or a method according to the method described inthis publication, and the compound [XXXXI], the compound [XXI], thecompound [XXIV], the compound [XX] and the compound [XXV] can beproduced by known methods or commercially available products can beused.

[0604] The present compounds have excellent herbicidal activity and someof them can exhibit excellent selectivity between crops and weeds. Inother words, the present compounds have herbicidal activity againstvarious weeds which may cause some trouble in the foliar treatment andsoil treatment on upland fields, such as listed below.

[0605] Onagraceous Weeds:

[0606] large-flowered eveningprimrose (Oenothera erythrosepala),

[0607] cutleaf eveningprimrose(Oenothera laciniata),

[0608] Ranunculaceous Weeds:

[0609] roughseeded buttercup (Ranunculus muricatus), hairy

[0610] buttercup (Ranunculus sardous)

[0611] Polygonaceous Weeds:

[0612] wild buckwheat (Polygonum convolvulus), pale smartweed (Polygonumlapathiolium), pennsylvania smartweed (Polygonum pensylvanicum),ladysthumb (Polygonum persicaria), curly dock (Rumex crispus), broadleafdock (Rumex obtusifolius), Japanese knotweed (Polygonum cuspidatum)

[0613] Portulacaceous Weeds:

[0614] common purslane (Portulaca oleracea)

[0615] Caryophyllaceous Weeds:

[0616] common chickweed (Stellaria media), sticky chickweed (Cerastiumglomeratum)

[0617] Chenopodiaceous Weeds:

[0618] common lambsquarters (Chenopodium album), kochia (Kochiascoparia)

[0619] Amaranthaceous Weeds:

[0620] redroot pigweed (Amaranthus retroflexus), smooth pigweed(Amaranthus hybridus)

[0621] Cruciferous (Brassicaceous) Weeds:

[0622] wild radish (Raphanus raphanistrum), wild mustard (Sinapisarvensis), shepherdpurse (Capsella bursa-pastoris), virginia pepperweed(Lepidium virginicum)

[0623] Leguminous (Fabaceous) Weeds:

[0624] hemp sesbania (Sesbania exaltata), sicklepod (Cassiaobtusifolia), Florida beggarweed (Desmodium tortuosum), white clover(Trifolium repens), common vetch (Vicia sativa), black medik (Medicagolupulina)

[0625] Malvaceous Weeds:

[0626] velvetleaf (Abutilon theophrasti), prickly sida (Sida spinosa)

[0627] Violaceous Weeds:

[0628] field pansy (Viola arvensis), wild pansy (Viola tricolor)

[0629] Rubiaceous Weeds:

[0630] catchweed bedstraw (cleavers) (Galium aparine)

[0631] Convolvulaceous Weeds:

[0632] ivyleaf morningglory (Ipomoea hederacea), tall morningglory(Ipomoea purpurea), entireleaf morningglory (Ipomoea hederacea var.integriuscula), pitted morningglory (Ipomoea lacunosa), field bindweed(Convolvulus arvensis)

[0633] Labiate Weeds:

[0634] red deadnettle (Lamium purpureum), henbit (Lamium amplexicaule)

[0635] Solanaceous Weeds:

[0636] jimsonweed (Datura stramonium), black nightshade (Solanum nigrum)

[0637] Scrophulariaceous Weeds:

[0638] birdseye speedwell (Veronica persica), corn speedwell (Veronicaarvensis), ivyleaf speedwell (Veronica hederaefolia)

[0639] Composite Weeds:

[0640] common cocklebur (Xanthium pensylvanicum), common sunflower(Helianthus annuus), wild camomille (Matricaria chamomilla), scentlesschamomile (Matricaria perforata or inodora), corn marigold(Chrysanthemum segetum), pineappleweed (Matricaria matricarioides),common ragweed (Ambrosia artemisiifolia), giant ragweed (Ambrosiatrifida), horseweed (Erigeron canadensis), Japanese mugwort (Artemisiaprinceps), tall goldenrod (Solidago altissima), common dandelion(Taraxacum officinale)

[0641] Boraginaceous Weeds:

[0642] forget-me-not (Myosotis arvensis)

[0643] Asclepiadaceous Weeds:

[0644] common milkweed (

[0645] Asclepias syriaca)

[0646] Euphorbiaceous Weeds:

[0647] sun spurge (Euphorbia helioscopia), spotted spurge (Euphorbiamaculata)

[0648] Geraniaceous Weeds:

[0649] Carolina geranium(Geranium carolinianum)

[0650] Oxalidaceous Weeds:

[0651] pink woodsorrel (Oxalis corymbosa)

[0652] Cucurbitaceous Weeds:

[0653] burcucumber (Sicyos angulatus)

[0654] Graminaceous Weeds:

[0655] barnyardgrass (Echinochloa crus-galli), green foxtail (Setariaviridis), giant foxtail (Setaria faberi), large crabgrass (Digitariasanguinalis), Southern Crabgrass (Digitaria ciliaris), goosegrass(Eleusine indica), annual bluegrass (Poa annua), blackgrass (Alopecurusmyosuroides), wild oat (Avena fatua), johnsongrass (Sorghum halepense),quackgrass (Agropyron repens), downy brome (Bromus tectorum),bermudagrass (Cynodon dactylon), fall panicum (Panicum dichotomiflorum),Texas panicum (Panicum texanum), shattercane (Sorghum vulgare), waterfoxtail (Alopecurus geniculatus)

[0656] Commelinaceous Weeds:

[0657] common dayflower (Commelina communis)

[0658] Equisetaceous Weeds:

[0659] field horsetail (Equisetum arvense)

[0660] Cyperaceous Weeds:

[0661] rice flatsedge (Cyperus iria), purple nutsedge (Cyperusrotundus), yellow nutsedge (Cyperus esculentus)

[0662] Furthermore, some of the present compounds exhibit no significantphytotoxicity on the main crops such as corn (Zea mays), wheat (Triticumaestivum), barley (Hordeum vulgare), rice (Oryza sativa), sorghum(Sorghum bicolor), soybean (Glycine max), cotton (Gossypium spp.), sugarbeet (Beta vulgaris), peanut (Arachis hypogaea), sunflower (Helianthusannuus), and canola (Brassica napus); horticultural crops such asflowers and ornamental plants; and vegetable crops. The presentcompounds can also attain the effective control of various weeds whichmay cause some trouble in the no-tillage cultivation of soybean (Glycinemax), corn (Zea mays), wheat (Triticum aestivum), and other crops.Furthermore, some of the present compounds exhibit no significantphytotoxicity on the crops.

[0663] The present compounds also have herbicidal activity againstvarious weeds which may cause some trouble in the flooding treatment onpaddy fields, such as listed below.

[0664] Graminaceous Weeds:

[0665] barnyardgrass (Echinochloa oryzicola)

[0666] Scrophulariaceous Weeds:

[0667] common falsepimpernel (Lindernia procumbens)

[0668] Lythraceous Weeds:

[0669] Indian toothcup (Rotala indica), red stem (Ammannia multiflora)

[0670] Elatinaceous Weeds:

[0671] waterwort (Elatine triandra)

[0672] Cyperaceous Weeds:

[0673] smallflower umbrella sedge (Cyperus difformis), hardstem bulrush(Scirpus juncoides), needle spikerush (Eleocharis acicularis), waternutgrass (Cyperus serotinus), water chestnut (Eleocharis kuroguwai)

[0674] Pontederiaceous Weeds:

[0675] monochoria (Monochoria vaginalis)

[0676] Alismataceous Weeds:

[0677] arrowhead (Sagittaria pygmaea), arrowhead (Sagittaria trifolia),waterplantain (Alisma canaliculatum)

[0678] Potamogetonaceous Weeds:

[0679] roundleaf pondweed (Potamogeton distinctus)

[0680] Potamogetonaceous Weeds:

[0681] roundleaf pondweed (Potamogeton distinctus)

[0682] Umbelliferous Weeds:

[0683] watercelery sp. (Oenanthe javanica)

[0684] Furthermore, some of the present compounds exhibit no significantphytotoxicity on transplanted paddy rice.

[0685] The present compounds can also attain the control of a widevariety of weeds which are growing or will grow in the orchards,grasslands, lawns, forests, waterways, canals, or other non-cultivatedlands in which weed controlling is necessiated such as levee, riverbed,roadside, railroad, green field of park, ground, parking, airport,industrial place (ex. factory, storage equipement), fallow land, vacantlot, and the like. The present compounds also have herbicidal activityagainst various aquatic weeds, such as water hyacinth (Eichhorniacrassipes), which are growing or will grow at the waterside such asrivers, canals, waterways or reservoir.

[0686] The present compounds have substantially the same characteristicsas those of the herbicidal compounds disclosed in the publishedspecification of International Patent Application, WO95/34659. In thecase where crops with tolerance imparted by introducing a herbicidetolerance gene described in the published specification are cultivated,the present compounds can be used at larger rates than those used whenordinary crops without tolerance are cultivated, which makes it possibleto control other unfavorable weeds more effectively.

[0687] When the present compounds are used as the active ingredients ofherbicides, they are usually mixed with solid or liquid carriers ordiluents, surfactants, and other auxiliary agents to give emulsifiableconcentrates, wettable powders, flowables, granules, concentratedemulsions, water-dispersible granules, or other formulations.

[0688] These formulations may contain any of the present compounds as anactive ingredient at an amount of 0.001 to 80% by weight, preferably0.005 to 70% by weight, based on the total weight of the formulation.

[0689] The solid carrier or diluent which can be used may include, forexample, fine powders or granules of the following materials: mineralmatters such as kaolin clay, attapulgite clay, bentonite, acid clay,pyrophyllite, talc, diatomaceous earth, and calcite; organic substancessuch as walnut shell powder; water-soluble organic substances such asurea; inorganic salts such as ammonium sulfate; and synthetic hydratedsilicon oxide. The liquid carrier or diluent which can be used mayinclude, for example, aromatic hydrocarbons such as methylnaphthalene,phenylxylylethane, and alkylbenzene (e.g., xylene); alcohols such asisopropanol, ethylene glycol, and 2-ethoxyethanol; esters such asphthalic acid dialkyl esters; ketones such as acetone, cyclohexanone,and isophorone; mineral oils such as machine oil; vegetable oils such assoybean oil and cottonseed oil; dimethyl sulfoxide,N,N-dimethylformamide, acetonitrile, N-methylpyrrolidone, and water.

[0690] The surfactant used for emulsification, dispersing, or spreadingmay include surfactants of the anionic type, such as alkylsulfates,alkylsulfonates, alkylarylsulfonates, dialkylsulfosuccinates, andphosphates of polyoxyethylene alkyl aryl ethers; and surfactants of thenonionic type, such as polyoxyethylene alkyl ethers, polyoxyethylenealkyl aryl ethers, polyoxyethylene polyoxypropylene block copolymers,sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acidesters.

[0691] The auxiliary agent may include lignin sulfonates, alginates,polyvinyl alcohol, gum arabic, CMC (carboxymethylcellulose), and PAP(isopropyl acid phosphate).

[0692] The present compounds are usually formulated as described aboveand then used for pre- or post-emergence soil, foliar, or floodingtreatment of weeds. The soil treatment may include soil surfacetreatment and soil incorporation. The foliar treatment may includeapplication over the plants and directed application in which a chemicalis applied only to weeds so as to keep off the crop plants.

[0693] The present compounds may often exhibit the enhancement ofherbicidal activity when used in admixture with other herbicides. Theycan also be used in admixture with insecticides, acaricides,nematocides, fungicides, bactericides, plant growth regulators,fertilizers, and soil conditioners.

[0694] Examples of the herbicide which can be used in admixture with thepresent compounds are atrazine, cyanazine, dimethametryn, metribuzin,prometryn, simazine, simetryn, chlorotoluron, diuron, fluometuron,isoproturon, linuron, methabenzthiazuron, propanil, bentazone,bromoxynil, ioxynil, pyridate, butamifos, dithiopyr, ethalfluralin,pendimethalin, thiazopyr, trifluralin, acetochlor, alachlor, butachlor,diethatyl-ethyl, dimethenamid, fluthiamide, mefenacet, metolachlor,pretilachlor, propachlor, cinmethylin, acifluorfen, acifluorfen-sodium,benzfendizone, bifenox, butafenacil, chlomethoxynil, fomesafen,lactofen, oxadiazon, oxadiargyl, oxyfluorfen, carfentrazone-ethyl,fluazolate, flumiclorac-pentyl, flumioxazine, fluthiacet-methyl,isopropazol, sulfentrazone, thidiazimin, azafenidin, pyraflufen-ethyl,cinidon-ethyl, difenzoquat, diquat, paraquat, 2,4-D, 2,4-DB, clopyralid,dicamba, fluroxypyr, MCPA, MCPB, mecoprop, quinclorac, triclopyr,azimsulfuron, bensulfuron-methyl, chlorimuron-ethyl, chlorsulfuron,cloransulam-methyl, cyclosulfamuron, diclosulam, ethoxysulfuron,flazasulfuron, flucarbazone, flumetsulam, flupyrsulfuron,halosulfuron-methyl, imazosulfuron, indosulfuron, metosulam,metsulfuron-methyl, nicosulfuron, oxasulfuron, primisulfuron-methyl,procarbazone-sodium, prosulfuron, pyrazosulfuron-ethyl, rimsulfuron,sulfometuron-methyl, sulfosulfuron, triasulfuron, tribenuron-methyl,tritosulfuron, thifensulfuron-methyl, triflusulfuron-methyl,pyribenzoxim, bispyribac-sodium, pyriminobac-methyl, pyrithiobac-sodium,imazameth, imazamethabenz-methyl, imazamox, imazapic, imazapyr,imazaquin, imazethapyr, tepraloxydim, alloxydim-sodium, clethodim,clodinafop-propargyl, dihalofop-butyl, dichlofop-methyl,fenoxaprop-ethyl, fenoxaprop-p-ethyl, fluazifop-buthyl,fluazifop-p-butyl, haloxyfop-methyl, quizalofop-p-ethyl, sethoxydim,tralkoxydim, diflufenican, flurtamone, norflurazone, benzofenap,isoxaflutole, pyrazolate, pyrazoxyfen, sulcotrione, clomazone,mesotrione, isoxachlortole, bialaphos, glufosinate-ammonium, glyphosate,sulfosate, dichlobenil, isoxaben, benthiocarb, butylate, dimepiperate,EPTC, esprocarb, molinate, pyributicarb, triallate, bromobutide, DSMA,MSMA, cafenstrol, daimron, epoprodan, flupoxam, metobenzuron,pentoxazone, piperophos, triaziflam,

[0695] beflubutamid, benzobicyclon, clomeprop, fentrazamide, flufenacet,florasulam, indanofan, isoxadifen, mesotrione, naploanilide,oxaziclomefone, pethoxyamid, phnothiol, pyridafol.

[0696] The above compounds are described in the catalog of FarmChemicals Handbook, 1995 (Meister Publishing Company); AG CHEM NEWCOMPOUND REVIEW, VOL. 13, 1995, VOL. 15, 1997, VOL.16, 1998 or,VOL.17,1999 (AG CHEM INFORMATION SERVICES); or Josouzai Kenkyu Souran(Hakuyu-sha).

[0697] When the present compounds are used as the active ingredients ofherbicides, the application amount, although it may vary with theweather conditions, formulation types, application times, applicationmethods, soil conditions, crops to be protected, weeds to be controlled,and other factors, is usually in the range of 0.01 to 20,000 g,preferably 1 to 12,000 g, per hectare. In the case of emulsifiableconcentrates, wettable powders, flowables, concentrated emulsions,water-dispersible granules, or other similar formulations, they areusually applied after diluted in their prescribed amounts with water (ifnecessary, containing an adjuvant such as a spreading agent) at a ratioof 10 to 1000 liters per hectare. In the case of granules or some typesof flowables, they are usually applied as such without any dilution.

[0698] The adjuvant which can be used, if necessary, may include, inaddition to the surfactants as described above, polyoxyethylene resinacids (esters), lignin sulfonates, abietates,dinaphthylmethanedisulfonates, crop oil concentrates, and vegetable oilssuch as soybean oil, corn oil, cottonseed oil, and sunflower oil.

[0699] The present compounds can also be used as the active ingredientsof harvesting aids such as defoliants and desiccants for cotton(Gossipyum spp.), and desiccants for potato (Solanum tuberosum). Inthese cases, the present compounds are usually formulated in the samemanner as the case where they are used as the active ingredients ofherbicides, and used alone or in admixture with other harvesting aidsfor foliar treatment before the harvesting of crops.

[0700] The following production examples, formulation examples and testexamples and the like will illustrate the present invention further indetail below, but do not limit the scope of the invention.

[0701] First, production examples of present compounds and productionexamples of intermediates will be shown. The compound numbers of presentcompounds correspond to numbers described in Tables 1 to 5 describedbelow.

PRODUCTION EXAMPLE 1 Production of Compound 1-1

[0702] 0.43 g of4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol(produced in Intermediate Production Example 1) was dissolved in 2.0 mlof N,N-dimethylformamide, and to this was added 0.15 g of anhydrouspotassium carbonate, and 0.17 g of methyl 2-bromopropionate was addedwith stirring at room temperature, then, the mixtures was stirred for 3hours at 70° C. The reaction solution was cooled to room temperature,then, the reaction solution was poured into ice water, and extractedwith ethyl acetate. The organic layer was washed with saturated saline,dried over anhydrous magnesium sulfate, and concentrated. The residueswas subjected to silica gel column chromatography to obtain 0.39 g ofmethyl2-[4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate[Compound 1-1 of the present invention].

[0703]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 1.61 (d, 3H, J=6.9 Hz), 3.52 (s,3H), 3.77 (s, 3H), 4.70 (q, 1H, J=6.7 Hz), 6.31 (s, 1H), 6.7 to 6.8 (m,1H), 6.8 to 6.9 (m, 2H), 6.9 to 7.0 (m, 2H), 7.36 (d, 1H, J=9.0 Hz)

PRODUCTION EXAMPLE 2 Production of Compound 2-1

[0704] 0.30 g of3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol(described later, produced in Intermediate Production Example 2) wasdissolved in 1.4 ml of N,N-dimethylformamide, and to this was added 0.10g of anhydrous potassium carbonate, and 0.11 g of methyl2-bromopropionate was added with stirring at room temperature, then, themixtures was stirred for 3 hours at 70° C. The reaction solution wascooled to room temperature, then, the reaction solution was poured intoice water, and extracted with ethyl acetate. The organic layer waswashed with saturated saline, dried over anhydrous magnesium sulfate,and concentrated. The residues was subjected to silica gel columnchromatography to obtain 0.28 g of methyl2-[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate[Compound 2-1 of the present invention].

[0705]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 1.60 (d, 3H, J=7.0 Hz), 3.53 (s,3H), 3.75 (s, 3H), 4.74 (q, 1H, J=6.7 Hz), 6.32 (s, 1H), 6.5 to 6.7 (m,3H), 6.9 to 7.0 (m, 1H), 7.1 to 7.3 (m, 1H), 7.38 (d, 1H, J=8.9 Hz)

PRODUCTION EXAMPLE 3 Production of Compound 3-1

[0706] 0.23 g of2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenolwas dissolved in 6 ml of N,N-dimethylformamide, and to this was added0.22 g of anhydrous potassium carbonate, and 0.13 g of methyl2-bromopropionate was added with stirring at room temperature, then, themixtures was stirred for 3 hours at 80° C. The reaction solution wascooled to room temperature, then, the reaction solution was poured intoice water, and extracted with ethyl acetate. The organic layer waswashed with saturated saline, dried over anhydrous magnesium sulfate,and concentrated. The residues was subjected to silica gel columnchromatography to obtain 0.23 g of methyl2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate[Compound 3-1 of the present invention].

[0707]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 1.47 (d, 3H, J=6.8 Hz), 3.50 (q,3H, J=0.7 Hz), 3.6 to 3.8 (m, 3H), 4.6 to 4.8 (m, 1H), 6.28 (s, 1H), 6.7to 6.8 (m, 1H), 6.8 to 6.9 (m, 1H), 6.9 to 7.1 (m, 1H), 7.1 to 7.2 (m,2H), 7.3 to 7.4 (m, 1H).

[0708] Physical values of present compounds produced in the same manneras in Production Example 3 are shown below.

[0709] Ethyl2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate[Compound 3-2 of the present invention].

[0710]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 1.23 (t, 3H, J=7.1 Hz), 1.47 (d,3H, J=6.8 Hz), 3.50 (s, 3H), 4.1 to 4.3 (m, 2H), 4.6 to 4.8 (m, 1H), 6.3to 6.4 (m, 1H), 6.7 to 7.0 (m, 3H), 7.0 to 7.2 (m, 2H), 7.3 to 7.4 (m,1H).

[0711] Methyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[Compound 3-11 of the present invention].

[0712] Melting Point: 116.4° C.

[0713] Ethyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[Compound 3-12 of the present invention].

[0714]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 1.26 (t, 3H, J=7.1 Hz), 3.50 (s,3H), 4.19 (q, 2H, J=7.2 Hz), 4.64 (s, 2H), 6.28 (s, 1H), 6.7 to 6.8 (m,1H), 6.9 to 7.2 (m, 4H), 7.36 (d, 1H, J=8.8 Hz).

PRODUCTION EXAMPLE 4 Production of Compound 3-189

[0715] Process 1:

[0716] 0.365 g of methyl2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate[Compound 3-1 of the present invention] was dissolved in 4 ml of1,4-dioxane, to this was added a mixed solution of 1 ml of conc.hydrochloric acid and 1 ml of water while stirring, then, the mixturewas heated for 5 hours and 45 minutes while stirring under refluxcondition. Thereafter, the solution was allowed to cool, and ice waterwas poured into the reaction solution, ethyl acetate and saturatedsaline were added to the solution which was separated subsequently, andaqueous sodium hydrogen carbonate was added to the organic layer beforeseparation, aqueous hydrochloric acid was added to the aqueous layer toacidify it, then, ethyl acetate was added before separation, the organiclayer was washed with saturated saline, and dried over magnesiumsulfate, then, concentrated to obtain 0.183 g of2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionicacid.

[0717]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 1.53 (d, 3H, J=6.9 Hz), 3.51 (s,3H), 4.76 to 4.83 (m, 1H), 6.32 (d, 1H, J=3.5 Hz), 6.63 to 6.67 (m, 1H),7.0 to 7.1 (m, 2H), 7.1 to 7.2 (m, 2H), 7.38 (d, 1H, J=9.0 Hz).

[0718] Process 2:

[0719]2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionicacid is dissolved in tetrahydrofuran, to this is added thionyl chloridewhile stirring, then, the mixture is heated while stirring under refluxcondition. Then, the solution is allowed to cool, concentrated, then,dissolved in tetrahydrofuran (hereinafter, referred to as Solution A).Tetrahydrofuran is added to 1-pentyl alcohol, and Solution A is added tothis, then, pyridine is added. The mixture is stirred at roomtemperature, then, 2% aqueous hydrochloric acid is poured into thereaction solution, and extracted with ethyl acetate. The organic layeris washed with saturated saline, and dried over magnesium sulfate, then,concentrated. The residue is subjected to silica gel columnchromatography (eluent: hexane/ethyl acetate=5/1) to obtain pentyl2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate[compound 3-189 of the present invention].

PRODUCTION EXAMPLE 5 Production of Compound 3-20

[0720] Process 1:

[0721] 0.4 g of methyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[Compound 3-11 of the present invention] was dissolved in 4 ml of1,4-dioxane, to this was added a mixed solution of 1 ml of conc.hydrochloric acid and 1 ml of water while stirring, then, the mixturewas heated for 12 hours while stirring under reflux condition.Thereafter, the solution was allowed to cool, and ice water was pouredinto the reaction solution, ethyl acetate and saturated saline wereadded to the solution which was separated subsequently, and aqueoussodium hydrogen carbonate was added to the organic layer beforeseparation, aqueous hydrochloric acid was added to the aqueous layer toacidify it, then, ethyl acetate was added before separation, the organiclayer was washed with saturated saline, and dried over magnesiumsulfate, then, concentrated to obtain 0.252 g of[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]aceticacid.

[0722]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 3.50 (d, 3H, J=1.2 Hz), 4.66 (s,2H), 6.31 (s, 1H), 6.69 (d, 1H, J=6.5 Hz), 6.98 to 7.20 (m, 4H), 7.38(d, 1H, J=8.8 Hz).

[0723] Process 2:

[0724] 1.0 g of[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]aceticacid was dissolved in tetrahydrofuran, to this was added 0.7 ml ofthionyl chloride while stirring, then, the mixture was heated whilestirring under reflux condition for 2 hours. Then, the solution wasallowed to cool, concentrated, then, dissolved in 3 ml oftetrahydrofuran (hereinafter, referred to as Solution B). 0.7 ml oftetrahydrofuran was added to 0.05 g of allyl alcohol, and trisectedportions of Solution B were added, then, 0.17 ml of pyridine was added.The mixture was stirred for 2 hours at room temperature, then, 2%aqueous hydrochloric acid was poured into the reaction solution, andextracted with ethyl acetate. The organic layer was washed withsaturated saline, and dried over magnesium sulfate, then, concentrated.The residue was subjected to silica gel column chromatography (eluent:hexane/ethyl acetate=5/1) to obtain 0.08 g of allyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[compound 3-20 of the present invention].

[0725]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.50 (d, 3H, J=1.2 Hz), 4.62 to4.64 (m, 2H), 4.68 (s, 2H), 5.22 to 5.32 (m, 2H), 5.8 to 6.0 (m, 1H),6.28 (s, 1H), 6.76 (d, 1H, J=6.5 Hz), 6.91 to 7.14 (m, 4H), 7.35 (d, 1H,J=8.6 Hz).

PRODUCTION EXAMPLE 6 Production of Compound 3-16

[0726] 0.20 g of2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenolwas dissolved in 2 ml of N,N-dimethylformamide, to this was added 0.083g of potassium carbonate, and the mixture was stirred at roomtemperature for 50 minutes. To this was added 0.077 g of t-butylchloroacetate, and the mixture was stirred for 2 hours at 40 to 60° C.After allowing to cool, ice water was poured into the reaction solution,ethyl acetate and saturated saline were added before separation. Theorganic layer was washed with saturated saline, dried over magnesiumsulfate and concentrated. The residue was subjected to silica gel columnchromatography (eluent: n-hexane/ethyl acetate=6/1) to obtain 0.39 g oft-butyl2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[compound 3-16 of the present invention].

[0727]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 1.44 (s, 9H), 3.49 (d, 3H, J=1.1Hz), 4.53 (s, 2H), 6.27 (s, 1H), 6.80 (d, 1H, J=6.6 Hz), 6.8 to 7.2 (m,4H), 7.35 (d, 1H, J=8.9 Hz).

[0728] Melting Point: 55.6° C.

PRODUCTION EXAMPLE 7 Production of Compound 3-198

[0729] 1.5 g of[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]aceticacid was dissolved in 6 ml of tetrahydrofuran, to this was added 1 ml ofthionyl chloride while stirring, and the mixture was stirred for 2 hoursand 10 minutes under reflux condition. Then, the solution was allowed tocool, concentrated, then, dissolved in 3 ml of tetrahydrofuran(hereinafter, referred to as Solution C). 1 ml of tetrahydrofuran wasadded to 0.273 g of isobutyl alcohol, and trisected portions of SolutionC were added, then, 0.25 ml of pyridine was added. Thereafter, themixture was stirred for 2 hours at room temperature, then, 2% aqueoushydrochloric acid was poured into the reaction solution, and ethylacetate was added before separation, the organic layer was washed withsaturated saline, and dried over magnesium sulfate, then, concentrated.The residue was subjected to silica gel column chromatography (eluent:hexane/ethyl acetate=6/1) to obtain 0.34 g of isobutyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[compound 3-198 of the present invention].

[0730]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 0.89 (d, 6H, J-6.7 Hz), 1.8 to 2.0(m, 1H), 3.50 (d, 3H, J=1.2 Hz), 3.92 (d, 2H, J=6.7 Hz), 4.67 (s, 2H),6.28 (s, 1H), 6.77 (d, 1H, J=6.6 Hz), 6.85 to 7.15 (m, 4H), 7.36 (d, 1H,J=8.9 Hz).

PRODUCTION EXAMPLE 8 Production of Compound 3-11

[0731] To 0.93 g of methyl[2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-4-fluorophenoxy}phenoxy]acetate,were added 10 ml of N,N-dimethylformamide and 0.31 g of potassiumcarbonate, then, 0.58 g of methyl iodide was added to the reactionsolution, and the mixture was stirred at room temperature for 2 hours.50 ml of diluted hydrochloric acid was added to the reaction solutionand extracted with ethyl acetate. The organic layer was washed withwater and then saturated saline, dried over anhydrous sodium sulfate,and concentrated under reduced pressure. The residue was subjected tosilica gel column chromatography to obtain 0.82 g of methyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[Compound 3-11 of the present invention].

[0732]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 3.49-3.50 (m, 3H), 3.73 (s, 3H),4.66 (s, 2H), 6.28 (s, 1H), 6.76 (d, 1H, J=6.6 Hz), 6.9-7.2 (m, 4H),7.36 (d, 1H, J=8.9 Hz).

PRODUCTION EXAMPLE 9 Production of Compound 3-12

[0733] To ethyl[2-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate,are added N,N-dimethylformamide and potassium carbonate, then, methyliodide is added to the reaction solution, and the mixture is stirred atroom temperature. Diluted hydrochloric acid is added to the reactionsolution and extracted with ethyl acetate. The organic layer is washedwith water and then saturated saline, and dried over anhydrous magnesiumsulfate, and concentrated. The residue is subjected to silica gel columnchromatography to obtain ethyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[compound 3-12 of the present invention].

PRODUCTION EXAMPLE 10 Production of Compound 1-2

[0734] 100 mg of4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol(produced in Intermediate Production Example 1) was dissolved in 1.0 mlof N,N-dimethylformamide, and to this was added 42 mg of anhydrouspotassium carbonate, and 46 mg of ethyl 2-bromopropionate was added withstirring at room temperature, then, the mixtures was stirred for 2 hoursat 60° C. The reaction solution was cooled to room temperature, then,the reaction solution was poured into ice water, and extracted withethyl acetate. The organic layer was washed with saturated saline, driedover anhydrous magnesium sulfate, and concentrated. The residue wassubjected to silica gel column chromatography to obtain 85 mg of ethyl2-[4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate[Compound 1-2 of the present invention].

[0735]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 1.27 (t, 3H, J=7.0 Hz), 1.60 (d,3H, J=6.9 Hz), 3.52 (s, 3H), 4.23 (q, 2H, J=7.0 Hz), 4.68 (q, 1H, J=6.9Hz), 6.31 (s, 1H), 6.7-6.8 (m, 1H), 6.8-6.9 (m, 2H), 6.9-7.0 (m, 2H),7.37 (d, 1H, J=8.9 Hz).

PRODUCTION EXAMPLE 11 Production of compound 1-11

[0736] 150 mg of4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol(described later, produced in Intermediate Production Example 1) wasdissolved in 1.0 ml of N,N-dimethylformamide, and to this was added 51mg of anhydrous potassium carbonate, and 50 mg of methyl bromoacetatewas added with stirring at room temperature, then, the mixtures wasstirred for 2 hours at 60° C. The reaction solution was cooled to roomtemperature, then, the reaction solution was poured into ice water, andextracted with ethyl acetate. The organic layer was washed withsaturated saline, dried over anhydrous magnesium sulfate, andconcentrated. The residue was subjected to silica gel columnchromatography to obtain 167 mg of methyl[4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[Compound 1-11 of the present invention].

[0737]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 3.52 (q, 3H, J=1.1 Hz), 3.81 (s,3H), 4.62 (s, 2H), 6.32 (s, 1H), 6.74 (d, 1H, J=6.6 Hz), 6.8-6.9 (m,2H), 6.9-7.0 (m, 2H), 7.37 (d, 1H, J=8.9 Hz).

PRODUCTION EXAMPLE 12 Production of Compound 2-11

[0738] 100 mg of3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol(described later, produced in Intermediate Production Example 2) wasdissolved in 1 ml of N,N-dimethylformamide, and to this was added 34 mgof anhydrous potassium carbonate, and 37 mg of methyl bromoacetate wasadded with stirring at room temperature, then, the mixtures was stirredfor 1 hours at 60° C. The reaction solution was cooled to roomtemperature, then, the reaction solution was poured into ice water, andextracted with ethyl acetate. The organic layer was washed withsaturated saline, dried over anhydrous magnesium sulfate, andconcentrated. The residue was subjected to silica gel columnchromatography to obtain 110 mg of methyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[Compound 2-11 of the present invention].

[0739]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.53 (q, 3H, J=0.9 Hz), 3.80 (s,3H), 4.61 (s, 2H), 6.32 (s, 1H), 6.60 (s, 1H), 6.6-6.7 (m, 2H), 6.92 (d,1H, J=6.6 Hz), 7.23 (d, 1H, J=7.9 Hz), 7.39 (d, 1H, J=9.0 Hz).

PRODUCTION EXAMPLE 13 Production of Compound 5-7

[0740] 72 mg of3-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol(described later, produced in Intermediate Production Example 9) wasdissolved in 1.0 ml of N,N-dimethylformamide, and to this was added 31mg of anhydrous potassium carbonate, and 31 mg of methyl2-bromopropionate was added with stirring at room temperature, then, themixtures was stirred for 1 hours at 70° C. The reaction solution wascooled to room temperature, then, the reaction solution was poured intowater, and extracted with ethyl acetate. The organic layer was washedwith saturated saline, dried over anhydrous magnesium sulfate, andconcentrated. The residue was subjected to silica gel columnchromatography to obtain 80 mg of methyl2-[3-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate[Compound 5-7 of the present invention].

[0741]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 1.62 (d, 3H, J=6.8 Hz), 3.53 (q,3H, J=1.4 Hz), 3.77 (s, 3H), 4.75 (q, 1H, J=6.8 Hz), 6.3-6.4 (m, 1H),6.6-6.8 (m, 3H), 6.8-6.9 (m, 1H), 7.2-7.3 (m, 1H), 7.53 (d, 1H, J=8.4Hz).

PRODUCTION EXAMPLE 14 Production of Compound 5-22

[0742] 32 mg of3-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol(described later, produced in Intermediate Production Example 9) wasdissolved in 0.5 ml of acetonitrile, and to this 13 mg of methylbromoacetate and 13 mg of anhydrous potassium carbonate were added,then, the mixtures was stirred for 1.5 hours at 60° C. The reactionsolution was cooled to room temperature, then, the reaction solution wassubjected to silica gel column chromatography to obtain 26 mg of methyl[3-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[Compound 5-22 of the present invention].

[0743]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.53 (q, 3H, J=1.0 Hz), 3.81 (s,3H), 4.63 (s, 2H), 6.32 (s, 1H), 6.6-6.7 (m, 1H), 6.7-6.8 (m, 2H), 6.85(d, 1H, J=5.9 Hz), 7.2-7.4 (m, 1H), 7.54 (d, 1H, J=8.4 Hz).

PRODUCTION EXAMPLE 15 Production of Compound 4-19

[0744] A mixture of 15.16 g of 2-(methoxycarbonyl)methoxyphenol, 29.23 gof2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene(produced in Intermediate Production Example 4), 11.5 g of anhydrouspotassium carbonate and 160 ml of N,N-dimethylformamide was stirred atroom temperature for 30 minutes, and then, stirred at 70° C. for 3hours. To the mixture, 5 g of 2-(methoxycarbonyl)methoxyphenol was addedand stirred for 1 hour. The reaction solution was poured into 2% ofaqueous hydrochloric acid solution and extracted with ethyl acetate. Theorganic layer was washed with saturated saline, dried over anhydrousmagnesium sulfate, and concentrated. The residue was subjected to silicagel column chromatography to obtain 17.8 g of2-{2-(methoxycarbonyl)methoxyphenoxy}-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene[Compound 4-19 of the present invention].

[0745]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.50 (q, 3H, J=1.0 Hz), 3.70 (s,3H), 4.63 (s, 2H), 6.28 (s, 1H), 6.88 (d, 1H, J=8.4 Hz), 6.93 (d, 1H,J=6.0 Hz), 7.0-7.1 (m, 1H), 7.1-7.3 (m, 2H), 7.87 (d, 1H, J=8.7 Hz).

PRODUCTION EXAMPLE 16 Production of Compound 3-11 of the PresentInvention

[0746] A mixture of 11.02 g of isoamyl nitrite and 45 ml of acetonitrilewas added dropwise to a mixture of 15.16 g of5-fluoro-2-{2-(methoxycarbonyl)methoxyphenoxy}-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline(produced in Intermediate Production Example 10), 6.21 g of copper (I)chloride, 12.65 g of copper (II) chloride, and 250 ml of acetonitrile atroom temperature, and the mixture was stirred for 2 hour. This reactionsolution was poured into 2% hydrochloric acid, and extracted with ethylacetate. The organic layer was washed with saturated saline, dried overanhydrous magnesium sulfate, and concentrated. The residue was subjectedto silica gel column chromatography to obtain 13 g of methyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[Compound 3-11 of the present invention].

PRODUCTION EXAMPLE 17 Production of Compound 4-20 of the PresentInvention

[0747] Methyl[2-{2,4-difluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[Compound 4-20 of the present invention] was produced from5-fluoro-2-{2-(methoxycarbonyl)methoxyphenoxy}-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline(produced in Intermediate Production Example 10) according to theprocess of production example 16.

[0748]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 3.52 (s, 3H,), 3.72 (s, 3H), 4.64(s, 2H), 6.32 (s, 1H), 6.8-7.2 (m, 6H)

PRODUCTION EXAMPLE 18 Production of Compound 4-21 of the PresentInvention

[0749] Methyl[2-{2-bromo-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[Compound 4-21 of the present invention] was produced from5-fluoro-2-{2-(methoxycarbonyl)methoxyphenoxy}-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline(produced in Intermediate Production Example 10) according to theprocess of production example 16.

[0750]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.53 (q, 3H, J=1.0 Hz), 3.72 (s,3H), 4.65 (s, 2H), 6.33 (s, 1H), 6.72 (d, 1H, J=6.4 Hz), 6.8-7.2 (m,4H), 7.53 (d, 1H, J=8.6 Hz).

PRODUCTION EXAMPLE 19 Production of Compound 4-22

[0751] Methyl[2-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxyacetate[Compound 4-22 of the present invention] was produced from Methyl[2-{2-bromo-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate[Compound 4-21] according to the forth process of Intermediateproduction example 9 described below.

[0752]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 3.49 (q, 3H, J=0.8 Hz), 3.71 (s,3H), 4.63 (s, 2H), 6.27 (s, 1H), 6.79 (d, 1H, J=5.8 Hz), 6.87 (d, 1H,J=8.1 Hz), 7.0-7.1 (m, 1H), 7.1-7.3 (m, 2H), 7.49 (d, 1H, J=8.4 Hz).

INTERMEDIATE PRODUCTION EXAMPLE 1 Production of4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol

[0753] First Process:

[0754] A mixture of 1.71 g of 4-benzyloxyphenol and 4.0 ml ofN,N-dimethylformamide was added dropwise into a mixture of 0.34 g ofsodium hydride and 8.5 ml of N,N-dimethylformamide while cooling withice, and the mixture was stirred for 20 minutes. A mixture of 3.0 g of2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene(described later, produced in Intermediate Production Example 4) and 7.0ml of N,N-dimethylformamide was added dropwise at the same temperature,and stirred for 1 hour. This reaction solution was poured into icewater, and extracted with ethyl acetate. The organic layer was washedonce with IN hydrochloric acid and once with saturated saline and driedover anhydrous magnesium sulfate, and concentrated. The residue wassubjected to silica gel column chromatography to obtain 2.0 g of2-(4-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.

[0755]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 3.51 (q, 3H, J=1.2 Hz), 5.04 (s,2H), 6.31 (s, 1H), 6.87 (d, 1H, J=5.9 Hz), 6.9 to 7.1 (m, 4H), 7.3 to7.5 (m, 5H), 7.84 (d, 1H, J=8.6 Hz).

[0756] Second Process:

[0757] To a mixture of 2.0 g of an iron powder, 6 ml of acetic acid and0.6 ml of water was added dropwise a solution of 1.9 g of2-(4-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzenein 5.0 ml of acetic acid, while maintaining the temperature of thereaction solution at 35° C. or lower. After completion of the addition,the mixture was stirred for 2 hours, then, the reaction solution wasfiltrated through Celite and diluted with ethyl acetate. The mixture wasneutralized with saturated aqueous sodium bicarbonate, the organic layerwas washed with saturated saline, dried over anhydrous magnesiumsulfate, and concentrated, then, the resulted residue was subjected tosilica gel column chromatography to obtain 1.0 g of2-(4-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline.

[0758]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 3.51 (q, 3H, J=1.3 Hz), 5.02 (s,2H), 6.30 (s, 1H), 6.58 (d, 1H, J=6.9 Hz), 6.62 (d, 1H, J=10.8 Hz), 7.3to 7.5 (m, 5H).

[0759] Third Process:

[0760] 0.46 g of isoamyl nitrite was added dropwise to a mixture of 1.0g of2-(4-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline,0.38 g of copper (I) chloride, 0.78 g of copper (II) chloride, and 14 mlof acetonitrile at room temperature, and the mixture was stirred for 1hour. This reaction solution was poured into 2% hydrochloric acid, andextracted with ethyl acetate. The organic layer was washed withsaturated saline, dried over anhydrous magnesium sulfate, andconcentrated. The residue was subjected to silica gel columnchromatography to obtain 0.73 g of([4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]methyl)benzene.

[0761]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.51 (s, 3H), 5.03 (s, 2H), 6.30(s, 1H), 6.74 (d, 1H, J=6.5 Hz), 6.9 to 7.0 (m, 4H), 7.2 to 7.5 (m, 6H).

[0762] Fourth Process:

[0763] To 0.72 g of([4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]methyl)benzene,were added 2 ml of ethyl acetate, 0.7 ml of ethanol and 36 mg of 10%palladium/carbon, and the mixture was stirred for 5 hours at roomtemperature under hydrogen atmosphere. The reaction system was purgedwith nitrogen, then, the reaction solution was filtrated through Celite,the filtrate was concentrated to obtain 0.48 g of4-{2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol.

[0764]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.51 (s, 3H), 5.2 to 5.5 (b, 1H),6.30 (s, 1H), 6.6 to 7.0 (m, 5H), 7.36 (d, 1H, J=9.0 Hz).

INTERMEDIATE PRODUCTION EXAMPLE 2 Production of3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol

[0765] First Process:

[0766] A mixture of 1.71 g of 3-benzyloxyphenol and 4.0 ml ofN,N-dimethylformamide was added dropwise into a mixture of 0.34 g ofsodium hydride and 8.5 ml of N,N-dimethylformamide while cooling withice, and the mixture was stirred for 20 minutes. A mixture of 3.0 g of2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene(described later, produced in Intermediate Production Example 4) and 7.0ml of N,N-dimethylformamide was added dropwise at the same temperature,and stirred for 1 hour. This reaction solution was poured into icewater, and extracted with ethyl acetate. The organic layer was washedonce with 1N hydrochloric acid and once with saturated saline, and driedover anhydrous magnesium sulfate, and concentrated. The residue wassubjected to silica gel column chromatography to obtain 2.4 g of2-(3-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.

[0767]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.53 (q, 3H, J=1.2 Hz), 5.03 (s,2H), 6.33 (s, 1H), 6.6 to 6.7 (m, 1H), 6.7 to 6.8 (m, 1H), 6.8 to 6.9(m, 1H), 7.01 (d, 1H, J=6.1 Hz), 7.2 to 7.5 (m, 6H), 7.87 (d, 1H, J=8.6Hz).

[0768] Second Process:

[0769] To a mixture of 2.5 g of an iron powder, 8 ml of acetic acid and0.8 ml of water was added dropwise a solution of 2.4 g of2-(3-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzenein 6.0 ml of acetic acid, while maintaining the temperature of thereaction solution at 35° C. or lower. After completion of the addition,the mixture was stirred for 2 hours, then, the reaction solution wasfiltrated through Celite and diluted with ethyl acetate. The mixture wasneutralized with saturated aqueous sodium bicarbonate, the organic layerwas washed with saturated saline, dried over anhydrous magnesiumsulfate, and concentrated, then, the resulted residue was subjected tosilica gel column chromatography to obtain 1.5 g of2-(3-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline.

[0770] Melting Point: 67.0° C.

[0771] Third Process:

[0772] 0.34 g of isoamyl nitrite was added dropwise to a mixture of 1.5g of2-(3-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline,0.57 g of copper (I) chloride, 1.17 g of copper (II) chloride, and 21 mlof acetonitrile at room temperature, and the mixture was stirred for 1hour. This reaction solution was poured into 2% hydrochloric acid, andextracted with ethyl acetate. The organic layer was washed withsaturated saline, dried over anhydrous magnesium sulfate, andconcentrated. The residue was subjected to silica gel columnchromatography to obtain 1.01 g of([3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]methyl)benzene.

[0773]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.53 (q, 3H, J=0.9 Hz), 5.03 (s,2H), 6.33 (s, 1H), 6.6 to 6.7 (m, 2H), 6.7 to 6.8 (m, 1H), 6.92 (d, 1H,J=6.5 Hz), 7.2 to 7.5 (m, 7H).

[0774] Fourth Process:

[0775] To 1.01 g of([3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]methyl)benzene,were added 3 ml of ethyl acetate, 1 ml of ethanol and 50 mg of 10%palladium/carbon, and the mixture was stirred for 5 hours at roomtemperature under hydrogen atmosphere. The reaction system was purgedwith nitrogen, then, the reaction solution was filtrated through Celite,the filtrate was concentrated to obtain 0.68 g of3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol.

[0776]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.52 (s, 3H), 5.5 to 5.8 (b, 1H),6.32 (s, 1H), 6.4 to 6.5 (m, 1H), 6.5 to 6.6 (m, 2H), 6.93 (d, 1H, J=6.7Hz), 7.17 (dd, 1H, J=8.3 Hz, 7.9 Hz), 7.38 (d, 1H, J=9.0 Hz).

INTERMEDIATE PRODUCTION EXAMPLE 3 Production of2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol

[0777] First Process:

[0778] A mixture of 4.05 g of 2-benzyloxyphenol and 9.5 ml ofN,N-dimethylformamide was added dropwise into a mixture of 0.80 g ofsodium hydride and 20 ml of N,N-dimethylformamide while cooling withice, and the mixture was stirred for 30 minutes. A mixture of 7.1 g of2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene(described later, produced in Intermediate Production Example 4) and 17ml of N,N-dimethylformamide was added dropwise at the same temperature,and stirred for 1 hour. This reaction solution was poured into icewater, and extracted with ethyl acetate. The organic layer was washedonce with 1N hydrochloric acid and once with saturated saline and driedover anhydrous magnesium sulfate, and concentrated. The residue wassubjected to silica gel column chromatography to obtain 8.6 g of2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.

[0779]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 3.52 (q, 3H, J=1.1 Hz), 5.01 (s,2H), 6.31 (s, 1H), 6.81 (d, 1H, J=6.0 Hz), 6.9 to 7.1 (m, 2H), 7.1 to7.4 (m, 7H), 7.78 (d, 1H, J=8.7 Hz).

[0780] Second Process:

[0781] To a of 8.6 g of an iron powder, 27 ml of acetic acid and 2.7 mlof water was added dropwise a solution of 8.6 g of2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzenein 23 ml of acetic acid, while maintaining the temperature of thereaction solution at 35° C. or lower. After completion of the addition,the mixture was stirred for 2 hours, then, the reaction solution wasfiltrated through Celite and diluted with ethyl acetate. The mixture wasneutralized with saturated aqueous sodium bicarbonate, the organic layerwas washed with saturated saline, dried over anhydrous magnesiumsulfate, and concentrated, then, the resulted residue was subjected tosilica gel column chromatography to obtain 6.46 g of2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline.

[0782]¹H-NMR (CDCl₃/250 MHz) (ppm): 3.50 (q, 3H, J=1.2 Hz), 5.06 (s,2H), 6.29 (s, 1H), 6.57 (dd, 1H, J=8.5, 1.6 Hz), 6.9 to 7.0 (m, 1H), 7.0to 7.1 (m, 3H), 7.2 to 7.4 (m, 6H).

[0783] Third Process:

[0784] 4.46 g of isoamyl nitrite was added dropwise to a mixture of 6.46g of2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline,2.45 g of copper (I) chloride, 5.04 g of copper (II) chloride, and 90 mlof acetonitrile at room temperature, and the mixture was stirred for 1hour. This reaction solution was poured into 2% hydrochloric acid, andextracted with ethyl acetate. The organic layer was washed withsaturated saline, dried over anhydrous magnesium sulfate, andconcentrated. The residue was subjected to silica gel columnchromatography to obtain 4.6 g of([2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]methyl)benzene.

[0785] Melting Point: 50.8° C.

[0786] Fourth Process:

[0787] To 4.5 g of([2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]methyl)benzene,were added 230 ml of ethyl acetate and 0.46 g of 10% palladium/carbon,and the mixture was stirred for 5 hours at room temperature underhydrogen atmosphere. The reaction system was purged with nitrogen, then,the reaction solution was filtrated through Celite, the filtrate wasconcentrated to obtain 3.57 g of2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol.

[0788] Melting Point: 55.4° C.

INTERMEDIATE PRODUCTION EXAMPLE 4 Production of2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene

[0789] 1.77 g of 2,4,5-trifluoronitrobenzene and 1.94 g of3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidine weredissolved in 10 ml of dimethyl sulfoxide, and 1.52 g of anhydrouspotassium carbonate was added to this at room temperature, then, themixture was stirred for 1 hour at 80° C. The reaction solution wasallowed to cool to room temperature, then, the reaction solution waspoured into ice water, and extracted with ethyl acetate. The organiclayer was washed with saturated saline, dried over anhydrous magnesiumsulfate, and concentrated. The residue was subjected to silica gelcolumn chromatography to obtain 1.51 g of 2,5difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.

[0790] Melting Point: 150° C.

INTERMEDIATE PRODUCTION EXAMPLE 5 Production of methyl[2-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate

[0791] First Process:

[0792] 2.73 g of 2-methoxyphenol and 5.5 g of potassium carbonate wereadded to 20 ml of N,N-dimethylformamide, and the mixture was heated to60%. Into this mixture was added dropwise a solution comprising 4.3 g ofN-(2,5-difluoro-4-nitrophenyl)acetamide and 30 ml ofN,N-dimethylformamide at temperature from 60 to 65° C. The temperatureof the mixture was kept for 1 hour while stirring, then, the mixture wascooled to room temperature, poured into water, extracted with ethylacetate, and the organic layer was washed with dilute hydrochloric acid,washed with water, dried over magnesium sulfate, and concentrated toobtain 5.52 g ofN-[2-fluoro-5-(2-methoxyphenoxy)-4-nitrophenyl]acetamide.

[0793]¹H-NMR (250 MHz, CDCl₃) δ (ppm): 2.16 (3H, s), 3.78 (3H, s), 6.85to 7.22 (4H, m), 7.75 to 7.83 (1H, br), 7.83 (1H, d, J=10.7 Hz), 8.04(1H, d, J=6.9 Hz).

[0794] Second Process:

[0795] 5.4 g of N-[2-fluoro-5-(2-methoxyphenoxy)-4-nitrophenyl]acetamidewas dissolved in 50 mol of methylene chloride, then, 4.7 g of borontribromide was added under ice cooling. The mixture was stirred for 2hours under the same temperature, conc. hydrochloric acid was added tothe solution and the resulted mixture was poured into water, extractedwith ethyl acetate, the organic layer was washed with water, dried overmagnesium sulfate, concentrated, and the resulted crystal was washedwith t-butyl methyl ether to obtain 3.2 g ofN-[2-fluoro-5-(2-hydroxyphenoxy)-4-nitrophenyl]acetamide.

[0796]¹H-NMR (300 MHz, CDCl₃) δ (ppm): 2.20 (3H, s), 6.33 (1H, bs), 6.86to 7.23 (4H, m), 7.63 (1H, bs), 7.81 (1H, d, J=10.3 Hz), 8.34 (1H, d,J=6.7 Hz).

[0797] Third Process:

[0798] 3.02 g ofN-[2-fluoro-5-(2-hydroxyphenoxy)-4-nitrophenyl]acetamide was dissolvedin 20 ml of N,N-dimethylformamide, then, 1.5 g of potassium carbonatewas added, and the mixture was stirred for 1 hour at room temperature.Then, 1.6 g of methyl bromoacetate was added at room temperature. Themixture was stirred for 2 hours under the same condition, poured intowater, extracted with ethyl acetate, and the organic layer was washedwith dilute hydrochloric acid, washed with water, dried over magnesiumsulfate and concentrated, and the resulted crystal was washed witht-butyl methyl ether to obtain 3.01 g of methyl[2-(5-acetylamino-4-fluoro-2-nitrophenoxy)phenoxy]acetate.

[0799]¹H-NMR (250 MHz, CDCl₃) δ (ppm): 2.16 (3H, s), 3.73 (3H, s), 4.62(2H, s), 6.95 to 7.26 (4H, m), 7.71 (1H, bs), 7.85 (1H, d, J=10.7 Hz),8.06 (1H, d, J=6.9 Hz).

[0800] Fourth Process:

[0801] Into a mixture of 40 ml of acetic acid and 40 ml of water wasadded 2.2 g of an iron powder, and the mixture was heated to 80° C. Intothe mixture was added 3.0 g of methyl[2-(5-acetylamino-4-fluoro-2-nitrophenoxy)phenoxy]acetate, and themixture was heated for 30 minutes under reflux. Thereafter, the mixturewas poured into water, extracted with ethyl acetate, the organic layerwas washed with water, and washed with saturated aqueous sodiumbicarbonate, dried over magnesium sulfate, and concentrated to obtain2.01 g of methyl[2-(5-acetylamino-2-amino-4-fluorophenoxy)phenoxy]acetate.

[0802]¹H-NMR (250 MHz, CDCl₃) δ (ppm): 2.11 (3H, s), 3.31 to 4.15 (2H,br), 3.76 (3H, s), 4.71 (2H, s), 6.54 (1H, d, J=11.9 Hz), 6.90 to 7.01(4H, m), 7.17 (1H, bs), 7.69 (1H, d, J=7.54 Hz).

[0803] Fifth Process:

[0804] To 30 ml of conc. hydrochloric acid was added 2.0 g of methyl[2-(5-acetylamino-2-amino-4-fluorophenoxy)phenoxy]acetate, and themixture was stirred for 1 hour at room temperature. Thereafter, amixture of 0.42 g of sodium nitrite and 3 ml of water was added underice cool. The mixture was stirred for 1 hour under the same condition,then, 40 ml of t-butyl methyl ether was added, then, 0.85 g of copper(I) chloride was added. The mixture was stirred for 30 minutes, then,water was added to this, and extracted with t-butyl methyl ether, andthe organic layer was washed with water, dried over magnesium sulfateand concentrated, and the resulted residue was purified by columnchromatography (eluent: hexane/ethyl acetate=2/1) to obtain 0.52 g ofmethyl [2-(5-acetylamino-2-chloro-4-fluorophenoxy)phenoxy]acetate.

[0805] Melting Point: 138.9° C.

[0806] Sixth Process:

[0807] Into 10 ml of boron trifluoride methanol complex•methanolsolution was added 0.25 g of methyl[2-(5-acetylamino-2-chloro-4-fluorophenoxy)phenoxy]acetate, and themixture was heated for 3 hours while stirring. Thereafter, the reactionsolution was concentrated, the residue was dissolved in ethyl acetate,and washed with saturated aqueous sodium bicarbonate, dried overmagnesium sulfate, and concentrated to obtain 0.2 g of methyl[2-(5-amino-2-chloro-4-fluorophenoxy)phenoxy]acetate [Intermediatecompound A3-22].

[0808]¹H-NMR (250 MHz, CDCl₃) δ (ppm): 3.74 (3H, s), 3.86 (2H, br), 4.70(2H, s), 6.36 (1H, d, J=8.21 Hz), 6.83 to 7.09 (5H, m).

[0809] Seventh Process:

[0810] Into a mixture of methyl[2-(5-amino-2-chloro-4-fluorophenoxy)phenoxy]acetate [Intermediatecompound A3-22], methyl chloroformate and tetrahydrofuran is addeddropwise pyridine, and the mixture is stirred at room temperature.Dilute hydrochloric acid is added to the reaction solution, and this isextracted with ethyl acetate. The organic layer is washed with saturatedsaline, dried over anhydrous magnesium sulfate, and concentrated toobtain methyl[2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenoxy)phenoxy]acetate[Intermediate compound A9-22].

[0811] Eighth Process:

[0812] To ethyl 3-amino-4,4,4-trifluorocrotonate are addedN,N-dimethylformamide and sodium hydride and the mixture is stirred at0° C. Thereafter, to the reaction solution is added a mixture of methyl[2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenoxy)phenoxy]acetate[Intermediate compound A9-22] and N,N-dimethylformamide, and the mixtureis stirred at 80° C. Then reaction solution is cooled to roomtemperature, then, poured into a mixture of hydrochloric acid and icewater, and the deposited crystal is collected by filtration to obtainmethyl[2-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate.

INTERMEDIATE PRODUCTION EXAMPLE 6 Production of ethyl[2-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate

[0813] First Process:

[0814] 1.1 g of catechol and 2.76 g of potassium carbonate were added to20 ml of N,N-dimethylformamide, and the mixture was heated to 60° C.Into this mixture was added dropwise a solution comprising 2.16 g ofN-(2,5-difluoro-4-nitrophenyl)acetamide and 10 ml ofN,N-dimethylformamide at temperatures from 65 to 70° C. The temperatureof the mixture was kept for 1 hour, then, the mixture was cooled to roomtemperature, poured into water, extracted with ethyl acetate, and theorganic layer was washed with dilute hydrochloric acid, washed withwater, dried over magnesium sulfate, concentrated, and the resultedcrystal was washed with t-butyl methyl ether to obtain 2.56 g ofN-[2-fluoro-5-(2-hydroxyphenoxy)-4-nitrophenyl]acetamide.

[0815]¹H-NMR (300 MHz, CDCl₃) δ (ppm): 2.20 (3H, s), 6.33 (1H, bs), 6.86to 7.23 (4H, m), 7.63 (1H, bs), 7.81 (1H, d, J=10.3 Hz), 8.34 (1H, d,J=6.7 Hz).

[0816] Second Process:

[0817] Into a mixture of 25 ml of acetic acid and 25 ml of water wasadded 9.5 g of an iron powder, and the mixture was heated to 80° C. Intothe mixture was added dropwise a solution composed of 10.0 g ofN-[2-fluoro-5-(2-hydroxyphenoxy)-4-nitrophenyl]acetamide and 100 ml ofethyl acetate. The mixture was heated for 1 hour under reflux, then,poured into water, extracted with ethyl acetate, the organic layer waswashed with water, and washed with saturated aqueous sodium bicarbonate,dried over magnesium sulfate, and concentrated to obtain 7.42 g ofN-[4-amino-2-fluoro-5-(2-hydroxyphenoxy)phenyl]acetamide.

[0818]¹H-NMR (250 MHz, CDCl₃) δ (ppm): 2.16 (3H, s), 6.48 (1H, d, J=11.6Hz), 6.74 to 6.78 (2H, m), 6.93 to 6.96 (2H, m), 7.35 (1H, bs), 7.47(1H, d, J=7.4 Hz).

[0819] Third Process:

[0820] 7.4 g of N-[4-amino-2-fluoro-5-(2-hydroxyphenoxy)phenyl]acetamidewas dissolved in 30 ml of acetonitrile, then, 5.42 g of copper (II)chloride was added and the mixture was stirred at room temperature. Tothis was added dropwise a solution composed of 4.16 g of t-butyl nitriteand 5 ml of acetonitrile around room temperature. The mixture wasstirred for 1 hour at room temperature, then, poured into water,extracted with ethyl acetate, the organic layer was washed with dilutehydrochloric acid, washed with water, dried over magnesium sulfate andconcentrated, and the resulted residue was purified by silica gel columnchromatography (eluent: hexane/ethyl acetate=2/1) to obtain 3.92 g ofN-[4-chloro-2-fluoro-5-(2-hydroxyphenoxy)phenyl]acetamide.

[0821]¹H-NMR (250 MHz, CDCl₃) δ (ppm): 2.19 (3H, s), 5.72 (1H, s), 6.70to 6.84 (2H, m), 7.01 to 7.03 (2H, m), 7.23 (1H, d, J=10.3 Hz), 7.34(1H, bs), 8.18 (2H, d, J=7.4 Hz).

[0822] Fourth Process:

[0823] N-[4-chloro-2-fluoro-5-(2-hydroxyphenoxy)phenyl]acetamide isdissolved in N,N-dimethylformamide, then, potassium carbonate is addedand the mixture is stirred at room temperature. Then, ethyl bromoacetateis added at room temperature. The mixture is stirred under the sametemperature, poured into water, extracted with ethyl acetate, theorganic layer is washed with dilute hydrochloric acid, washed withwater, dried over magnesium sulfate and concentrated, and the resultedcrystal is washed with t-butyl methyl ether to obtain ethyl[2-(5-acetylamino-2-chloro-4-fluorophenoxy)phenoxy]acetate.

[0824] Fifth Process:

[0825] Into a boron trifluoride methanol complex methanol solution isadded ethyl [2-(5-acetylamino-2-chloro-4-fluorophenoxy)phenoxy]acetate,and the mixture is heated while stirring. Thereafter, the reactionsolution is concentrated, the residue is dissolved in ethyl acetate, andwashed with saturated aqueous sodium bicarbonate, dried over magnesiumsulfate, and concentrated to obtain ethyl[2-(5-amino-2-chloro-4-fluorophenoxy)phenoxy]acetate [Intermediatecompound A3-23].

[0826] Sixth Process:

[0827] Into a mixture of ethyl[2-(5-amino-2-chloro-4-fluorophenoxy)phenoxy]acetate [Intermediatecompound A3-23], ethyl chloroformate and tetrahydrofuran is addeddropwise pyridine, and the mixture is stirred at room temperature.Dilute hydrochloric acid is added to the reaction solution, and this isextracted with ethyl acetate. The organic layer is washed with saturatedsaline, dried over anhydrous magnesium sulfate, and concentrated toobtain ethyl[2-(2-chloro-4-fluoro-5-ethoxycarbonylaminophenoxy)phenoxy]acetate[Intermediate compound A8-23].

[0828] Seventh Process:

[0829] To ethyl 3-amino-4,4,4-trifluorocrotonate are addedN,N-dimethylformamide and sodium hydride and the mixture is stirred at0° C. Thereafter, to the reaction solution is added a mixture of ethyl[2-(2-chloro-4-fluoro-5-ethoxycarbonylaminophenoxy)phenoxy]acetate[Intermediate compound A8-23] and N,N-dimethylformamide, and the mixtureis stirred at 80° C. Then reaction solution is cooled to roomtemperature, then, poured into a mixture of hydrochloric acid and icewater, and the deposited crystal is collected by filtration to obtainethyl[2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-4-fluorophenoxy}phenoxy]acetate.s

INTERMEDIATE PRODUCTION EXAMPLE 7 Production of ethyl[2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-4-fluorophenoxy}phenoxy]acetate

[0830] First Process:

[0831] Into a mixture of ethyl[2-(5-amino-2-chloro-4-fluorophenoxy)phenoxy]acetate [Intermediatecompound A3-23], trichloromethyl chloroformate and toluene is addeddropwise activated carbon, and the mixture is heated under reflux. Thereaction solution is filtrated and the solvent is distilled off toobtain 4-chloro-2-fluoro-5-{2-(ethoxycarbonylmethoxy)phenoxy}phenylisocyanate [Intermediate compound A12-23].

[0832] Second Process:

[0833] To ethyl 3-amino-4,4,4-trifluorocrotonate are addedN,N-dimethylformamide and sodium hydride and the mixture is stirred at0° C. Thereafter, to the reaction solution is added a mixture of4-chloro-2-fluoro-5-{2-(ethoxycarbonylmethoxy)phenoxy}phenyl isocyanate[Intermediate compound A12-23] and N,N-dimethylformamide, and themixture is stirred at room temperature. The reaction solution is pouredinto a mixture of hydrochloric acid and ice water, and the depositedcrystal is collected by filtration to obtain ethyl[2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-4-fluorophenoxy}phenoxy]acetate.

INTERMEDIATE PRODUCTION EXAMPLE 8 Production of methyl[2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-4-fluorophenoxy}phenoxy]acetate

[0834]

[0835] First Process: Production of Compound [2h] from Compound [1h]

[0836] A solution consisting of 4.85 g of compound [1h], 2.88 g of ethyltrifluoroacetoacetate and 40 ml of toluene was subjected to azeotropicreaction with removing ethanol by passing through molecular sieves 5Afor 6 hours. After cooling, 50 ml of ethyl acetate was added to thereaction mixture, then, the organic layer was washed with concentratedhydrochloric acid, water and saturated saline, dried over anhydroussodium sulfate, and concentrated under reduced pressure. The residue waswashed with hexane to obtain 5.82 g of crude compound [2h].

[0837] m.p.: 165.3° C.

[0838] Second Process: Production of Compound [3h] from Compound [2h]

[0839] To a solution of 1.0 g of the crude compound [2h] and 3 ml oftetrahydrofuran, 4 ml of acetic acid and 0.87 g of potassium cyanatewere added, and the mixture was stirred at room temperature for 6 hours,then, heated under reflux at 120° C. for 2 hours. After cooling, 30 mlof water was added to the reaction mixture and the mixture was extractedwith ethyl acetate. The organic layer was washed with saturated aqueoussodium bicarbonate solution, water and saturated saline, and then, driedover anhydrous sodium sulfate, and concentrated under reduced pressure.The residue was subjected to silica gel column chromatography to obtain0.67 g of compound [3 h].

[0840]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 3.72 (3H, s), 4.65 (2H, s), 6.16(1H, s), 6.77 (1H, d, J=6.6 Hz), 6.89-7.15 (4H, m), 7.36 (1H, d, J=8.9Hz).

[0841] ethyl[2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-4-fluorophenoxy}phenoxy]acetateis produced from ethyl[2-(5-amino-2-chloro-4-fluorophenoxy)phenoxy]acetate [Intermediatecompound A3-23] according to the process of Intermediate ProductionExample 8.

INTERMEDIATE PRODUCTION EXAMPLE 9 Production of3-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol

[0842] First Process:

[0843] The mixture of 3.53 g of 3-methoxyphenol, 5.12 g of anhydrouspotassium carbonate, 10 g of2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzen(described above, produced in Intermediate Production Example 4) and 40ml of N,N-dimethylformamide was stirred at 60 to 70° C. for 2 hours. Thereaction mixture was poured into the mixture of aqueous hydrochloricacid solution and ice water and extracted with ethyl acetate. Theorganic layer was washed with saturated saline, dried over anhydrousmagnesium sulfate, and concentrated. The residue was subjected to silicagel column chromatography to obtain 4.17 g of5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.

[0844]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 3.53 (q, 3H, J=1.2 Hz), 3.79 (s,3H), 6.33 (s, 1H), 6.6-6.7 (m, 2H), 6.7-6.8 (m, 1H), 7.00 (d, 1H, J=6.1Hz), 7.2-7.3 (m, 1H), 7.88 (d, 1H, J=8.6 Hz)

[0845] Second Process:

[0846] A solution of 4.17 g of5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzenein 10 ml of acetic acid was added dropwise over 20 minutes to a mixtureof 4.5 g of iron powder, 10 ml of acetic acid and 1 ml of water. Afterthe addition, the mixture was stirred for 2 hours, filtered throughcelite and diluted with ethyl acetate. The resultant was washed withwater 2 times, the organic layer was washed with saturated aqueoussodium bicarbonate solution and saturated saline, dried over anhydrousmagnesium sulfate, and concentrated. The residue was subjected to silicagel column chromatography to obtain 3.67 g of5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline.

[0847]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.52 (q, 3H, J=1.0 Hz), 3.76 (s,3H), 4.0-4.2 (b, 2H), 6.31 (s, 1H), 6.5-6.7 (m, 4H), 6.73 (d, 1H, J=7.0Hz), 7.1-7.3 (m, 1H).

[0848] Third Process:

[0849] To a mixture of 213 mg of5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline,93 mg of copper(I) bromide and 1 ml of acetonitrile, 57 mg of t-butylnitrite was added dropwise over 1 hour at 0° C. The mixture was stirredfor 30 minutes, then, stirred at room temperature and stirred for 10hours. The reaction mixture was poured into 2% hydrochloric acid andextracted with ethyl acetate. The organic layer was washed withsaturated saline, dried over anhydrous magnesium sulfate, andconcentrated. The residue was subjected to silica gel columnchromatography to obtain 75 mg of5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]bromobenzene.

[0850]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.52 (q, 3H, J=1.2 Hz), 3.77 (s,3H), 6.31 (s, 1H), 6.5-6.6 (m, 1H), 6.59 (s. 1H), 6.6-6.7 (m, 1H), 6.86(d, 1H, J=6.7 Hz), 7.22 (dd, 1H, J=9.0, 8.7 Hz), 7.54 (d, 1H, J=8.8 Hz).

[0851] Forth Process:

[0852] A mixture of 75 mg of5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]bromobenzene,27 mg of copper cyanide and 0.5 ml of N-methyl-2-pyrrolidone was stirredat 170 to 180° C. for 2 hours. The reaction mixture was cooled to roomtemperature, water was added to the mixture and the resultant wasextracted with ethyl acetate. The organic layer was dried over anhydrousmagnesium sulfate, and concentrated. The residue was subjected to silicagel column chromatography to obtain 57 mg of5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]cyanobenzene.

[0853]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.52 (q, 3H, J=1.0 Hz), 3.79 (s,3H), 6.31 (s, 1H), 6.31 (s. 1H), 6.67 (s, 1H), 6.6-6.7 (m, 1H), 6.7-6.8(m, 1H), 6.84 (d, 1H, J=5.8 Hz), 7.29 (dd, 1H, J=9.1, 8.6 Hz), 7.53 (d,1H, J=8.4 Hz).

[0854] Fifth Process:

[0855] To a solution of 57 mg of5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]cyanobenzenein 0.6 ml of chloroform, 48 μl of boron tribromide was added dropwise at0° C. After the addition, the temperature of the reaction mixture wasraised to room temperature and stirred for 1 hour. The mixture wascooled to 0° C. and 1 ml of methanol was added thereto. The solvent wasremoved under reduced pressure, the resultant was diluted with ethylacetate, and then, saturated aqueous sodium bicarbonate solution wasadded thereto to be pH 4. The resultant was extracted with ethylacetate. The organic layer was washed with saturated saline, dried overanhydrous magnesium sulfate, and concentrated. The residue was subjectedto silica gel column chromatography to obtain 36 mg of3-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol.

[0856]¹H-NMR (CDCl₃/300 MHz) δ (ppm): 3.52 (q, 3H, J=1.0 Hz), 6.32 (s,1H), 6.3-6.5 (b, 1H), 6.5-6.6 (m, 1H), 6.6-6.7 (m, 2H), 6.87 (d, 1H,J=5.8 Hz), 7.21 (dd, 1H, J=8.3, 8.1 Hz), 7.51 (d, 1H, J=8.4 Hz).

INTERMEDIATE PRODUCTION EXAMPLE 10 Production of5-fluoro-2-(2-(methoxycarbonyl)methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline

[0857] To a solution of 19 g of iron powder, 60 ml of acetic acid and 6ml of water, a solution of 19.12 g of5-fluoro-2-{2-(methoxycarbonyl)methoxyphenoxy}-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene[Compound 4-19 of the present invention] in 60 ml of acetic acid wasadded dropwise under ice cooling. After the addition, the temperature ofthe reaction mixture was raised to room temperature and the mixture wasstirred for 4 hours. The reaction mixture was filtered with sellaite anddiluted with ethyl acetate. The dilution was washed with water,saturated aqueous sodium bicarbonate solution and saturated saline,dried over anhydrous magnesium sulfate, and concentrated. The residuewas subjected to silica gel column chromatography to obtain 15.16 g of5-fluoro-2-{2-(methoxycarbonyl)methoxyphenoxy}-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline.

[0858]¹H-NMR (CDCl₃/250 MHz) δ (ppm): 3.51 (q, 3H, J=0.9 Hz), 3.76 (s,3H), 4.2-4.4 (b, 2H), 4.69 (s, 2H), 6.29 (s, 1H), 6.6-6.7 (m, 2H),6.9-7.1 (m, 4H).

INTERMEDIATE PRODUCTION EXAMPLE 11 Production of methyl[2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenoxy)phenoxy]acetate[Intermediate compound A9-22]

[0859] First Process:

[0860] 4-chloro-2-fluoro-5-(2-hydroxyphenoxy)aniline [IntermediateCompound A3-4] was produced fromN-[4-chloro-2-fluoro-5-(2-hydroxyphenoxy)phenyl]acetamide (produced inIntermediate Production Example 6,Third Process) according to theprocess of Sixth Process of Intermediate Production Example 5 .

[0861]¹H-NMR(CDCl₃/300 MHz) δ (ppm): 3.76 (bs, 2H), 5.78 (bs, 1H), 6.41(d, 1H, J=8.3 Hz), 6.7-6.9 (m, 2H), 7.0-7.1 (m, 2H), 7.09 (d, 1H, J=10.2Hz).

[0862] Second Process:

[0863] Into a mixture of 4-chloro-2-fluoro-5-(2-hydroxyphenoxy)aniline[Intermediate Compound A3-4], methyl chloroformate and tetrahydrofuranis added dropwise N,N-dimethylaniline, and the mixture is stirred atroom temperature. Dilute hydrochloric acid is added to the reactionsolution, and this is extracted with ethyl acetate. The organic layer iswashed with saturated saline, dried over anhydrous magnesium sulfate,and concentrated to obtain2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenoxy)phenol [Intermediatecompound A9-4].

[0864] Third Process:

[0865] 2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenoxy)phenol[Intermediate compound A9-4] is dissolved in N,N-dimethylformamide,then, potassium carbonate is added, and the mixture is stirred for 1hour at room temperature. Then, methyl bromoacetate is added at roomtemperature. The mixture is stirred at 60° C. for 2 hours, poured intowater, extracted with ethyl acetate, and the organic layer is washedwith dilute hydrochloric acid and water, dried over magnesium sulfateand concentrated to obtain methyl[2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenoxy)phenoxy]acetate[Intermediate compound A9-22].

[0866] Next, some compounds of the present invention will beexemplified. Specific compounds are specified by compound numbersdescribed in Tables 1 to 5. The compounds of the present invention arenot limited to these exemplified compounds.

[0867] Compound [I-1] (compound numbers are described in Table 1) TABLE1 [I-1]

Compound No X³ X⁴ A 1-1 H H OCH(CH₃)CO₂CH₃ 1-2 H H OCH(CH₃)CO₂CH₂CH₃ 1-3H H OCH(CH₃)CO₂CH₂CH₂CH₃ 1-4 H H OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 1-5 H HOCH(CH₃)CO₂CH(CH₃)₂ 1-6 H H OCH(CH₃)CO₂C(CH₃)₃ 1-7 H HOCH(CH₃)CO₂CH₂CH₂F 1-8 H H OCH(CH₃)CO₂CH₂CH₂Cl 1-9 H HOCH(CH₃)CO₂CH₂CCl₃ 1-10 H H OCH(CH₃)CO₂CH₂CH═CH₂ 1-11 H H OCH₂CO₂CH₃1-12 H H OCH₂CO₂CH₂CH₃ 1-13 H H OCH₂CO₂CH₂CH₂CH₃ 1-14 H HOCH₂CO₂CH₂CH₂CH₂CH₃ 1-15 H H OCH₂CO₂CH(CH₃)₂ 1-16 H H OCH₂CO₂C(CH₃)₃1-17 H H OCH₂CO₂CH₂CH₂F 1-18 H H OCH₂CO₂CH₂CH₂Cl 1-19 H H OCH₂CO₂CH₂CCl₃1-20 H H OCH₂CO₂CH₂CH═CH₂ 1-21 H H SCH(CH₃)CO₂CH₃ 1-22 H HSCH(CH₃)CO₂CH₂CH₃ 1-23 H H SCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 1-24 H HSCH(CH₃)CO₂CH₂CH₂CH₃ 1-25 H H SCH(CH₃)CO₂CH(CH₃)₂ 1-26 H HSCH(CH₃)CO₂C(CH₃)₃ 1-27 H H SCH(CH₃)CO₂CH₂CH₂F 1-28 H HSCH(CH₃)CO₂CH₂CH₂Cl 1-29 H H SCH(CH₃)CO₂CH₂CCl₃ 1-30 H HSCH(CH₃)CO₂CH₂CH═CH₂ 1-31 H H SCH₂CO₂CH₃ 1-32 H H SCH₂CO₂CH₂CH₃ 1-33 H HSCH₂CO₂CH₂CH₂CH₃ 1-34 H H SCH₂CO₂CH₂CH₂CH₂CH₃ 1-35 H H SCH₂CO₂CH(CH₃)₂1-36 H H SCH₂CO₂C(CH₃)₃ 1-37 H H SCH₂CO₂CH₂CH₂F 1-38 H H SCH₂CO₂CH₂CH₂Cl1-39 H H SCH₂CO₂CH₂CCl₃ 1-40 H H SCH₂CO₂CH₂CH═CH₂ 1-41 3-CH₃ HOCH(CH₃)CO₂CH₃ 1-42 3-CH₃ H OCH(CH₃)CO₂CH₂CH₃ 1-43 3-CH₃ HOCH(CH₃)CO₂CH₂CH₂CH₃ 1-44 3-CH₃ H OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 1-45 3-CH₃ HOCH(CH₃)CO₂CH(CH₃)₂ 1-46 3-CH₃ H OCH(CH₃)CO₂C(CH₃)₃ 1-47 3-CH₃ HOCH(CH₃)CO₂CH₂CH₂F 1-48 3-CH₃ H OCH(CH₃)CO₂CH₂CH₂Cl 1-49 3-CH₃ HOCH(CH₃)CO₂CH₂CCl₃ 1-50 3-CH₃ H OCH(CH₃)CO₂CH₂CH═CH₂ 1-51 3-CH₃ HOCH₂CO₂CH₃ 1-52 3-CH₃ H OCH₂CO₂CH₂CH₃ 1-53 3-CH₃ H OCH₂CO₂CH₂CH₂CH₃ 1-543-CH₃ H OCH₂CO₂CH₂CH₂CH₂CH₃ 1-55 3-CH₃ H OCH₂CO₂CH(CH₃)₂ 1-56 3-CH₃ HOCH₂CO₂C(CH₃)₃ 1-57 3-CH₃ H OCH₂CO₂CH₂CH₂F 1-58 3-CH₃ H OCH₂CO₂CH₂CH₂Cl1-59 3-CH₃ H OCH₂CO₂CH₂CCl₃ 1-60 3-CH₃ H OCH₂CO₂CH₂CH═CH₂ 1-61 2-CH₃ HOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 1-62 2-CH₃ H OCH(CH₃)CO₂CH₃ 1-63 2-CH₃ HOCH(CH₃)CO₂CH₂CH₃ 1-64 2-CH₃ H OCH(CH₃)CO₂CH₂CH₂CH₃ 1-65 2-CH₃ HOCH(CH₃)CO₂CH(CH₃)₂ 1-66 2-CH₃ H OCH(CH₃)CO₂C(CH₃)₃ 1-67 2-CH₃ HOCH(CH₃)CO₂CH₂CH₂F 1-68 2-CH₃ H OCH(CH₃)CO₂CH₂CH₂Cl 1-69 2-CH₃ HOCH(CH₃)CO₂CH₂CCl₃ 1-70 2-CH₃ H OCH(CH₃)CO₂CH₂CH═CH₂ 1-71 2-CH₃ HOCH₂CO₂CH₂CH₂CH₂CH₃ 1-72 2-CH₃ H OCH₂CO₂CH₃ 1-73 2-CH₃ H OCH₂CO₂CH₂CH₃1-74 2-CH₃ H OCH₂CO₂CH₂CH₂CH₃ 1-75 2-CH₃ H OCH₂CO₂CH(CH₃)₂ 1-76 2-CH₃ HOCH₂CO₂C(CH₃)₃ 1-77 2-CH₃ H OCH₂CO₂CH₂CH₂F 1-78 2-CH₃ H OCH₂CO₂CH₂CH₂Cl1-79 2-CH₃ H OCH₂CO₂CH₂CCl₃ 1-80 2-CH₃ H OCH₂CO₂CH₂CH═CH₂ 1-81 3-OCH₃ HOCH(CH₃)CO₂CH₃ 1-82 3-OCH₃ H OCH(CH₃)CO₂CH₂CH₃ 1-83 3-OCH₃ HOCH(CH₃)CO₂CH₂CH₂CH₃ 1-84 3-OCH₃ H OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 1-85 3-OCH₃ HOCH(CH₃)CO₂CH(CH₃)₂ 1-86 3-OCH₃ H OCH(CH₃)CO₂C(CH₃)₃ 1-87 3-OCH₃ HOCH(CH₃)CO₂CH₂CH₂F 1-88 3-OCH₃ H OCH(CH₃)CO₂CH₂CH₂Cl 1-89 3-OCH₃ HOCH(CH₃)CO₂CH₂CCl₃ 1-90 3-OCH₃ H OCH(CH₃)CO₂CH₂CH═CH₂ 1-91 3-OCH₃ HOCH₂CO₂CH₃ 1-92 3-OCH₃ H OCH₂CO₂CH₂CH₃ 1-93 3-OCH₃ H OCH₂CO₂CH₂CH₂CH₃1-94 3-OCH₃ H OCH₂CO₂CH₂CH₂CH₂CH₃ 1-95 3-OCH₃ H OCH₂CO₂CH(CH₃)₂ 1-963-OCH₃ H OCH₂CO₂C(CH₃)₃ 1-97 3-OCH₃ H OCH₂CO₂CH₂CH₂F 1-98 3-OCH₃ HOCH₂CO₂CH₂CH₂Cl 1-99 3-OCH₃ H OCH₂CO₂CH₂CCl₃ 1-100 3-OCH₃ HOCH₂CO₂CH₂CH═CH₂ 1-101 2-OCH₃ H OCR(CH₃)CO₂CH₃ 1-102 2-OCH₃ HOCH(CH₃)CO₂CH₂CH₃ 1-103 2-OCH₃ H OCH(CH₃)CO₂CH₂CH₂CH₃ 1-104 2-OCH₃ HOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 1-105 2-OCH₃ H OCH(CH₃)CO₂CH(CH₃)₂ 1-106 2-OCH₃H OCR(CH₃)CO₂C(CH₃)₃ 1-107 2-OCH₃ H OCR(CH₃)CO₂CH₂CH₂F 1-108 2-OCH₃ HOCH(CH₃)CO₂CH₂CH₂Cl 1-109 2-OCH₃ H OCH(CH₃)CO₂CH₂CCl₃ 1-110 2-OCH₃ HOCR(CH₃)CO₂CH₂CH═CH₂ 1-111 2-OCH₃ H OCH₂CO₂CH₃ 1-112 2-OCH₃ HOCH₂CO₂CH₂CH₃ 1-113 2-OCH₃ H OCH₂CO₂CH₂CH₂CH₃ 1-114 2-OCH₃ HOCH₂CO₂CH₂CH₂CH₂CH₃ 1-115 2-OCH₃ H OCH₂CO₂CH(CH₃)₂ 1-116 2-OCH₃ HOCH₂CO₂C(CH₃)₃ 1-117 2-OCH₃ H OCH₂CO₂CH₂CH₂F 1-118 2-OCH₃ HOCH₂CO₂CH₂CH₂Cl 1-119 2-OCH₃ H OCH₂CO₂CH₂CCl₃ 1-120 2-OCH₃ HOCH₂CO₂CH₂CH═CH₂ 1-121 3-Cl H OCH(CH₃)CO₂CH₃ 1-122 3-Cl ROCH(CH₃)CO₂CH₂CH₃ 1-123 3-Cl H OCH(CH₃)CO₂CH₂CH₂CH₃ 1-124 3-Cl HOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 1-125 3-Cl H OCH(CH₃)CO₂CH(CH₃)₂ 1-126 3-Cl HOCH(CH₃)CO₂C(CH₃)₃ 1-127 3-Cl H OCH(CH₃)CO₂CH₂CH₂F 1-128 3-Cl HOCH(CH₃)CO₂CH₂CH₂Cl 1-129 3-Cl H OCH(CH₃)CO₂CH₂CCH₃ 1-130 3-Cl HOCH(CH₃)CO₂CH₂CH═CH₂ 1-131 3-Cl H OCH₂CO₂CH₃ 1-132 3-Cl H OCH₂CO₂CH₂CH₃1-133 3-Cl H OCH₂CO₂CH₂CH₂CH₃ 1-134 3-Cl H OCH₂CO₂CH₂CH₂CH₂CH₃ 1-1353-Cl H OCH₂CO₂CH(CH₃)₂ 1-136 3-Cl H OCH₂CO₂C(CH₃)₃ 1-137 3-Cl HOCH₂CO₂CH₂CH₂F 1-138 3-Cl H OCH₂CO₂CH₂CH₂Cl 1-139 3-Cl H OCH₂CO₂CH₂CCl₃1-140 3-Cl H OCH₂CO₂CH₂CH═CH₂ 1-141 2-Cl H OCH(CH₃)CO₂CH₃ 1-142 2-Cl HOCH(CH₃)CO₂CH₂CH₃ 1-143 2-Cl H OCH(CH₃)CO₂CH₂CH₂CH₃ 1-144 2-Cl HOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 1-145 2-Cl H OCH(CH₃)CO₂CH(CH₃)₂ 1-146 2-Cl HOCH(CH₃)CO₂C(CH₃)₃ 1-147 2-Cl H OCH(CH₃)CO₂CH₂CH₂F 1-148 2-Cl HOCH(CH₃)CO₂CH₂CH₂Cl 1-149 2-Cl H OCH(CH₃)CO₂CH₂CCl₃ 1-150 2-Cl HOCH(CH₃)CO₂CH₂CH═CH₂ 1-151 2-Cl H OCH₂CO₂CH₃ 1-152 2-Cl H OCH₂CO₂CH₂CH₃1-153 2-Cl H OCH₂CO₂CH₂CH₂CH₃ 1-154 2-Cl H OCH₂CO₂CH₂CH₂CH₂CH₃ 1-1552-Cl H OCH₂CO₂CH(CH₃)₂ 1-156 2-Cl H OCH₂CO₂C(CH₃)₃ 1-157 2-Cl HOCH₂CO₂CH₂CH₂F 1-158 2-Cl H OCH₂CO₂CH₂CH₂Cl 1-159 2-Cl H OCH₂CO₂CH₂CCl₃1-160 2-Cl H OCH₂CO₂CH₂CH═CH₂ 1-161 H H NHCH(CH₃)CO₂CH₃ 1-162 H HNHCH(CH₃)CO₂CH₂CH₃ 1-163 H H NHCH(CH₃)CO₂CH₂CH₂CH₃ 1-164 H HNHCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 1-165 H H NHCH(CH₃)CO₂CH(CH₃)₂ 1-166 H HNHCH(CH₃)CO₂C(CH₃)₃ 1-167 H H NHCH(CH₃)CO₂CH₂CH₂F 1-168 H HNHCH(CH₃)CO₂CH₂CH₂Cl 1-169 H H NHCH(CH₃)CO₂CH₂CCl₃ 1-170 H HNHCH(CH₃)CO₂CH₂CH═CH₂ 1-171 H H NHCH₂CO₂CH₃ 1-172 H H NHCH₂CO₂CH₂CH₃1-173 H H NHCH₂CO₂CH₂CH₂CH₃ 1-174 H H NHCH₂CO₂CH₂CH₂CH₂CH₃ 1-175 H HNHCH₂CO₂CH(CH₃)₂ 1-176 H H NHCH₂CO₂C(CH₃)₃ 1-177 H H NHCH₂CO₂CH₂CH₂F1-178 H H NHCH₂CO₂CH₂CH₂Cl 1-179 H H NHCH₂CO₂CH₂CCl₃ 1-180 H HNHCH₂CO₂CH₂CH₂CH₂ 1-181 H H N(CH₃)CH(CH₃)CO₂CH₃ 1-182 H HN(CH₃)CH(CH₃)CO₂CH₂CH₃ 1-183 H H N(CH₃)CH₂CO₂CH₃ 1-184 H HN(CH₃)CH₂CO₂CH₂CH₃ 1-185 H H N(CH₃)CH₂CO₂CH₂CH₂CH₃ 1-186 H HOCH(CH₃)CO₂CH₂CH₂CH═CH₂ 1-187 H H OCH(CH₃)CO₂CH₂CH(CH₃)₂ 1-188 H HOCH(CH₃)CO₂CH(CH₃)CH₂CH₃ 1-189 H H OCH(CH₃)CO₂CH₂CH₂CH₂CH₂CH₃ 1-190 H HOCH(CH₃)CO₂CH₂CH₂CH(CH₃)₂ 1-191 H H OCH(CH₃)CO₂CH₂CH(CH₃)CH₂CH₃ 1-192 HH OCH(CH₃)CO₂CH(CH₃)CH₂CH₂CH₃ 1-193 H H OCH(CH₃)CO₂C(CH₃)₂CH₂CH₃ 1-194 HH OCH(CH₃)CO₂CH(CH₃)CH(CH₃)₂ 1-195 H H OCH(CH₃)CO₂CH₂C(CH₃)₃ 1-196 H HOCH(CH₃)CO₂CH₂C≡CH 1-197 H H OCH(CH₃)CO₂CH₂CH₂CH═CH₂ 1-198 H HOCH₂CO₂CH₂CH(CH₃)₂ 1-199 H H OCH₂CO₂CH(CH₃)CH₂CH₃ 1-200 H HOCH₂CO₂CH₂CH₂CH₂CH₂CH₃ 1-201 H H OCH₂CO₂CH₂C≡CH

[0868] Compound of the general formula (1-2] (compound numbers aredescribed in Table 2) TABLE 2 [I-2]

Compound No X³ X⁴ A 2-1 H H OCH(CH₃)CO₂CH₃ 2-2 H H OCH(CH₃)CO₂CH₂CH₃ 2-3H H OCH(CH₃)CO₂CH₂CH₂CH₃ 2-4 H H OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 2-5 H HOCH(CH₃)CO₂CH(CH₃)₂ 2-6 H H OCH(CH₃)CO₂C(CH₃)₃ 2-7 H HOCH(CH₃)CO₂CH₂CH₂F 2-8 H H OCH(CH₃)CO₂CH₂CH₂Cl 2-9 H HOCH(CH₃)CO₂CH₂CCl₃ 2-10 H H OCH(CH₃)CO₂CH₂CH═CH₂ 2-11 H H OCH₂CO₂CH₃2-12 H H OCH₂CO₂CH₂CH₃ 2-13 H H OCH₂CO₂CH₂CH₂CH₃ 2-14 H HOCH₂CO₂CH₂CH₂CH₂CH₃ 2-15 H H OCH₂CO₂CH(CH₃)₂ 2-16 H H OCH₂CO₂C(CH₃)₃2-17 H H OCH₂CO₂CH₂CH₂F 2-18 H H OCH₂CO₂CH₂CH₂Cl 2-19 H H OCH₂CO₂CH₂CCL32-20 H H OCH₂CO₂CH₂CHCH₂ 2-21 H H SCH(CH₃)CO₂CH₃ 2-22 H HSCH(CH₃)CO₂CH₂CH₃ 2-23 H H SCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 2-24 H HSCH(CH₃)CO₂CH₂CH₂CH₃ 2-25 H H SCH(CH₃)CO₂CH(CH₃)₂ 2-26 H HSCH(CH₃)CO₂C(CH₃)₃ 2-27 H H SCH(CH₃)CO₂CH₂CH₂F 2-28 H HSCH(CH₃)CO₂CH₂CH₂Cl 2-29 H H SCH(CH₃)CO₂CH₂CCl₃ 2-30 H HSCH(CH₃)CO₂CH₂CH═CH₂ 2-31 H H SCH₂CO₂CH₃ 2-32 H H SCH₂CO₂CH₂CH₃ 2-33 H HSCH₂CO₂CH₂CH₂CH₃ 2-34 H H SCH₂CO₂CH₂CH₂CH₂CH₃ 2-35 H H SCH₂CO₂CH(CH₃)₂2-36 H H SCH₂CO₂C(CH₃)₃ 2-37 H H SCH₂CO₂CH₂CH₂F 2-38 H H SCH₂CO₂CH₂CH₂Cl2-39 H H SCH₂CO₂CH₂CCl₃ 2-40 H H SCH₂CO₂CH₂CH═CH₂ 2-41 4-CH₃ HOCH(CH₃)CO₂CH₃ 2-42 4-CH₃ H OCH(CH₃)CO₂CH₂CH₃ 2-43 4-CH₃ HOCH(CH₃)CO₂CH₂CH₂CH₃ 2-44 4-CH₃ H OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 2-45 4-CH₃ HOCH(CH₃)CO₂CH(CH₃)₂ 2-46 4-CH₃ H OCH(CH₃)CO₂C(CH₃)₃ 2-47 4-CH₃ HOCH(CH₃)CO₂CH₂CH₂F 2-48 4-CH₃ H OCH(CH₃)CO₂CH₂CH₂Cl 2-49 4-CH₃ HOCH(CH₃)CO₂CH₂CCl₃ 2-50 4-CH₃ H OCH(CH₃)CO₂CH₂CH═CH₂ 2-51 4-CH₃ HOCH₂CO₂CH₃ 2-52 4-CH₃ H OCH₂CO₂CH₂CH₃ 2-53 4-CH₃ H OCH₂CO₂CH₂CH₂CH₃ 2-544-CH₃ H OCH₂CO₂CH₂CH₂CH₂CH₃ 2-55 4-CH₃ H OCH₂CO₂CH(CH₃)₂ 2-56 4-CH₃ HOCH₂CO₂C(CH₃)₃ 2-57 4-CH₃ H OCH₂CO₂CH₂CH₂F 2-58 4-CH₃ H OCH₂CO₂CH₂CH₂Cl2-59 4-CH₃ H OCH₂CO₂CH₂CCl₃ 2-60 4-CH₃ H OCH₂CO₂CH₂CH═CH₂ 2-61 2-CH₃ HOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 2-62 2-CH₃ H OCH(CH₃)CO₂CH₃ 2-63 2-CH₃ HOCH(CH₃)CO₂CH₂CH₃ 2-64 2-CH₃ H OCH(CH₃)CO₂CH₂CH₂CH₃ 2-65 2-CH₃ HOCH(CH₃)CO₂CH(CH₃)₂ 2-66 2-CH₃ H OCH(CH₃)CO₂C(CH₃)₃ 2-67 2-CH₃ HOCH(CH₃)CO₂CH₂CH₂F 2-68 2-CH₃ H OCH(CH₃)CO₂CH₂CH₂Cl 2-69 2-CH₃ HOCH(CH₃)CO₂CH₂CCl₃ 2-70 2-CH₃ H OCH(CH₃)CO₂CH₂CH═CH₂ 2-71 2-CH₃ HOCH₂CO₂CH₂CH₂CH₂CH₃ 2-72 2-CH₃ H OCH₂CO₂CH₃ 2-73 2-CH₃ H OCH₂CO₂CH₂CH₃2-74 2-CH₃ H OCH₂CO₂CH₂CH₂CH₃ 2-75 2-CH₃ H OCH₂CO₂CH(CH₃)₂ 2-76 2-CH₃ HOCH₂CO₂C(CH₃)₃ 2-77 2-CH₃ H OCH₂CO₂CH₂CH₂F 2-78 2-CH₃ H OCH₂CO₂CH₂CH₂Cl2-79 2-CH₃ H OCH₂CO₂CH₂CCl₃ 2-80 2-CH₃ H OCH₂CO₂CH₂CH═CH₂ 2-81 4-OCH₃ HOCH(CH₃)CO₂CH₃ 2-82 4-OCH₃ H OCH(CH₃)CO₂CH₂CH₃ 2-83 4-OCH₃ HOCH(CH₃)CO₂CH₂CH₂CH₃ 2-84 4-OCH₃ H OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 2-85 4-OCH₃ HOCH(CH₃)CO₂CH(CH₃)₂ 2-86 4-OCH₃ H OCH(CH₃)CO₂C(CH₃)₃ 2-87 4-OCH₃ HOCH(CH₃)CO₂CH₂CH₂F 2-88 4-OCH₃ H OCH(CH₃)CO₂CH₂CH₂Cl 2-89 4-OCH₃ HOCH(CH₃)CO₂CH₂CCl₃ 2-90 4-OCH₃ H OCH(CH₃)CO₂CH₂CH═CH₂ 2-91 4-OCH₃ HOCH₂CO₂CH₃ 2-92 4-OCH₃ H OCH₂CO₂CH₂CH₃ 2-93 4-OCH₃ H OCH₂CO₂CH₂CH₂CH₃2-94 4-OCH₃ H OCH₂CO₂CH₂CH₂CH₂CH₃ 2-95 4-OCH₃ H OCH₂CO₂CH(CH₃)₂ 2-964-OCH₃ H OCH₂CO₂C(CH₃)₃ 2-97 4-OCH₃ H OCH₂CO₂CH₂CH₂F 2-98 4-OCH₃ HOCH₂CO₂CH₂CH₂Cl 2-99 4-OCH₃ H OCH₂CO₂CH₂CCl₃ 2-100 4-OCH₃ HOCH₂CO₂CH₂CH═CH₂ 2-101 2-OCH₃ H OCH(CH₃)CO₂CH₃ 2-102 2-OCH₃ HOCH(CH₃)CO₂CH₂CH₃ 2-103 2-OCH₃ H OCH(CH₃)CO₂CH₂CH₂CH₃ 2-104 2-OCH₃ HOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 2-105 2-OCH₃ H OCH(CH₃)CO₂CH(CH₃)₂ 2-106 2-OCH₃H OCH(CH₃)CO₂C(CH₃)₃ 2-107 2-OCH₃ H OCH(CH₃)CO₂CH₂CH₂F 2-108 2-OCH₃ HOCH(CH₃)CO₂CH₂CH₂Cl 2-109 2-OCH₃ H OCH(CH₃)CO₂CH₂CCl₃ 2-110 2-OCH₃ HOCH(CH₃)CO₂CH₂CH═CH₂ 2-111 2-OCH₃ H OCH₂CO₂CH₃ 2-112 2-OCH₃ HOCH₂CO₂CH₂CH₃ 2-113 2-OCH₃ H OCH₂CO₂CH₂CH₂CH₃ 2-114 2-OCH₃ HOCH₂CO₂CH₂CH₂CH₂CH₃ 2-115 2-OCH₃ H OCH₃CO₂CH(CH₃)₂ 2-116 2-OCH₃ HOCH₂CO₂C(CH₃)₃ 2-117 2-OCH₃ H OCH₂CO₂CH₂CH₂F 2-118 2-OCH₃ HOCH₂CO₂CH₂CH₂Cl 2-119 2-OCH₃ H OCH₂CO₂CH₂CCl₃ 2-120 2-OCH₃ HOCH₂CO₂CH₂CH═CH₂ 2-121 4-Cl H OCH(CH₃)CO₂CH₃ 2-122 4-Cl HOCH(CH₃)CO₂CH₂CH₃ 2-123 4-Cl H OCH(CH₃)CO₂CH₂CH₂CH₃ 2-124 4-Cl HOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 2-125 4-Cl H OCH(CH₃)CO₂CH(CH₃)₂ 2-126 4-Cl HOCH(CH₃)CO₂C(CH₃)₃ 2-127 4-Cl H OCH(CH₃)CO₂CH₂CH₂F 2-128 4-Cl HOCH(CH₃)CO₂CH₂CH₂Cl 2-129 4-Cl H OCH(CH₃)CO₂CH₂CCl₃ 2-130 4-Cl HOCH(CH₃)CO₂CH₂CH═CH₂ 2-131 4-Cl H OCH₂CO₂CH₃ 2-132 4-Cl H OCH₂CO₂CH₂CH₃2-133 4-Cl H OCH₂CO₂CH₂CH₂CH₃ 2-134 4-Cl H OCH₂CO₂CH₂CH₂CH₂CH₃ 2-1354-Cl H OCH₂CO₂CH(CH₃)₂ 2-136 4-Cl H OCH₂CO₂C(CH₃)₃ 2-137 4-Cl HOCH₂CO₂CH₂CH₂F 2-138 4-Cl H OCH₂CO₂CH₂CH₂Cl 2-139 4-Cl H OCH₂CO₂CH₂CCl₃2-140 4-Cl H OCH₂CO₂CH₂CH═CH₂ 2-141 2-Cl H OCH(CH₃)CO₂CH₃ 2-142 2-Cl HOCH(CH₃)CO₂CH₂CH₃ 2-143 2-Cl H OCH(CH₃)CO₂CH₂CH₂CH₃ 2-144 2-Cl HOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 2-145 2-Cl H OCH(CH₃)CO₂CH(CH₃)₂ 2-146 2-Cl HOCH(CH₃)CO₂C(CH₃)₃ 2-147 2-Cl H OCH(CH₃)CO₂CH₂CH₂F 2-148 2-Cl HOCH(CH₃)CO₂CH₂CH₂Cl 2-149 2-Cl H OCH(CH₃)CO₂CH₂CCl₃ 2-150 2-Cl HOCH(CH₃)CO₂CH₂CH═CH₂ 2-151 2-Cl H OCH₂CO₂CH₃ 2-152 2-Cl H OCH₂CO₂CH₂CH₃2-153 2-Cl H OCH₂CO₂CH₂CH₂CH₃ 2-154 2-Cl H OCH₂CO₂CH₂CH₂CH₂CH₃ 2-1552-Cl H OCH₂CO₂CH(CH₃)₂ 2-156 2-Cl H OCH₂CO₂C(CH₃)₃ 2-157 2-Cl HOCH₂CO₂CH₂CH₂F 2-158 2-Cl H OCH₂CO₂CH₂CH₂Cl 2-159 2-Cl H OCH₂CO₂CH₂CCl₃2-160 2-Cl H OCH₂CO₂CH₂CH═CH₂ 2-161 H H NHCH(CH₃)CO₂CH₃ 2-162 H HNHCH(CH₃)CO₂CH₂CH₃ 2-163 H H NHCH(CH₃)CO₂CH₂CH₂CH₃ 2-164 H HNHCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 2-165 H H NHCH(CH₃)CO₂CH(CH₃)₂ 2-166 H HNHCH(CH₃)CO₂C(CH₃)₃ 2-167 H H NHCH(CH₃)CO₂CH₂CH₂F 2-168 H HNHCH(CH₃)CO₂CH₂CH₂Cl 2-169 H H NHCH(CH₃)CO₂CH₂CCl₃ 2-170 H HNHCH(CH₃)CO₂CH₂CH═CH₂ 2-171 H H NHCH₂CO₂CH₃ 2-172 H H NHCH₂CO₂CH₂CH₃2-173 H H NHCH₂CO₂CH₂CH₂CH₃ 2-174 H H NHCH₂CO₂CH₂CH₂CH₂CH₃ 2-175 H HNHCH₂CO₂CH(CH₃)₂ 2-176 H H NHCH₂CO₂C(CH₃)₃ 2-177 H H NHCH₂CO₂CH₂CH₂F2-178 H H NHCH₂CO₂CH₂CH₂Cl 2-179 H H NHCH₂CO₂CH₂CCl₃ 2-180 H HNHCH₂CO₂CH₂CH═CH₂ 2-181 H H N(CH₃)CH(CH₃)CO₂CH₃ 2-182 H HN(CH₃)CH(CH₃)CO₂CH₂CH₃ 2-183 H H N(CH₃)CH₂CO₂CH₃ 2-184 H HN(CH₃)CH₂CO₂CH₂CH₃ 2-185 H H N(CH₃)CH₂CO₂CH₂CH₂CH₃ 2-186 H HOCH(CH₃)CO₂CH₂CH₂CH═CH₂ 2-187 H H OCH(CH₃)CO₂CH₂CH(CH₃)₂ 2-188 H HOCH(CH₃)CO₂CH(CH₃)CH₂CH₃ 2-189 H H OCH(CH₃)CO₂CH₂CH₂CH₂CH₂CH₃ 2-190 H HOCH(CH₃)CO₂CH₂CH₂CH(CH₃)₂ 2-191 H H OCH(CH₃)CO₂CH₂CH(CH₃)CH₂CH₃ 2-192 HH OCH(CH₃)CO₂CH(CH₃)CH₂CH₂CH₃ 2-193 H H OCH(CH₃)CO₂C(CH₃)₂CH₂CH₃ 2-194 HH OCH(CH₃)CO₂CH(CH₃)CH(CH₃)₂ 2-195 H H OCH(CH₃)CO₂CH₂C(CH₃)₃ 2-196 H HOCH(CH₃)CO₂CH₂C═CH 2-197 H H OCH(CH₃)CO₂CH₂CH₂CH═CH₂ 2-198 H HOCH₂CO₂CH₂CH(CH₃)₂ 2-199 H H OCH₂CO₂CH(CH₃)CH₂CH₃ 2-200 H HOCH₂CO₂CH₂CH₂CH₂CH₂CH₃ 2-201 H H OCH₂CO₂CH₂C≡CH

[0869] Compound of the general formula [1-3] (compound numbers aredescribed in Table 3) TABLE 3 [I-3]

Compound No X³ X⁴ A 3-1 H H OCH(CH₃)CO₂CH₃ 3-2 H H OCH(CH₃)CO₂CH₂CH₃ 3-3H H OCH(CH₃)CO₂CH₂CH₂CH₃ 3-4 H H OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 3-5 H HOCH(CH₃)CO₂CH(CH₃)₂ 3-6 H H OCH(CH₃)CO₂C(CH₃)₃ 3-7 H HOCH(CH₃)CO₂CH₂CH₂F 3-8 H H OCH(CH₃)CO₂CH₂CH₂Cl 3-9 H HOCH(CH₃)CO₂CH₂CCl₃ 3-10 H H OCH(CH₃)CO₂CH₂CH═CH₂ 3-11 H H OCH₂CO₂CH₃3-12 H H OCH₂CO₂CH₂CH₃ 3-13 H H OCH₂CO₂CH₂CH₂CH₃ 3-14 H HOCH₂CO₂CH₂CH₂CH₂CH₃ 3-15 H H OCH₂CO₂CH(CH₃)₂ 3-16 H H OCH₂CO₂C(CH₃)₃3-17 H H OCH₂CO₂CH₂CH₂F 3-18 H H OCH₂CO₂CH₂CH₂Cl 3-19 H H OCH₂CO₂CH₂CCl₃3-20 H H OCH₂CO₂CH₂CH═CH₂ 3-21 H H SCH(CH₃)CO₂CH₃ 3-22 H HSCH(CH₃)CO₂CH₂CH₃ 3-23 H H SCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 3-24 H HSCH(CH₃)CO₂CH₂CH₂CH₃ 3-25 H H SCH(CH₃)CO₂CH(CH₃)₂ 3-26 H HSCH(CH₃)CO₂C(CH₃)₃ 3-27 H H SCH(CH₃)CO₂CH₂CH₂F 3-28 H HSCH(CH₃)CO₂CH₂CH₂Cl 3-29 H H SCH(CH₃)CO₂CH₂CCl₃ 3-30 H HSCH(CH₃)CO₂CH₂CH═CH₂ 3-31 H H SCH₂CO₂CH₃ 3-32 H H SCH₂CO₂CH₂CH₃ 3-33 H HSCH₂CO₂CH₂CH₂CH₃ 3-34 H H SCH₂CO₂CH₂CH₂CH₂CH₃ 3-35 H H SCH₂CO₂CH(CH₃)₂3-36 H H SCH₂CO₂C(CH₃)₃ 3-37 H H SCH₂CO₂CH₂CH₂F 3-38 H H SCH₂CO₂CH₂CH₂Cl3-39 H H SCH₂CO₂CH₂CCl₃ 3-40 H H SCH₂CO₂CH₂CH═CH₂ 3-41 3-CH₃ HOCH(CH₃)CO₂CH₃ 3-42 3-CH₃ H OCH(CH₃)CO₂CH₂CH₃ 3-43 3-CH₃ HOCH(CH₃)CO₂CH₂CH₂CH₃ 3-44 3-CH₃ H OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 3-45 3-CH₃ HOCH(CH₃)CO₂CH(CH₃)₂ 3-46 3-CH₃ H OCH(CH₃)CO₂C(CH₃)₃ 3-47 3-CH₃ HOCH(CH₃)CO₂CH₂CH₂F 3-48 3-CH₃ H OCH(CH₃)CO₂CH₂CH₂Cl 3-49 3-CH₃ HOCH(CH₃)CO₂CH₂CCl₃ 3-50 3-CH₃ H OCH(CH₃)CO₂CH₂CH═CH₂ 3-51 3-CH₃ HOCH₂CO₂CH₃ 3-52 3-CH₃ H OCH₂CO₂CH₂CH₃ 3-53 3-CH₃ H OCH₂CO₂CH₂CH₂CH₃ 3-543-CH₃ H OCH₂CO₂CH₂CH₂CH₂CH₃ 3-55 3-CH₃ H OCH₂CO₂CH(CH₃)₂ 3-56 3-CH₃ HOCH₂CO₂C(CH₃)₃ 3-57 3-CH₃ H OCH₂CO₂CH₂CH₂F 3-58 3-CH₃ H OCH₂CO₂CH₂CH₂Cl3-59 3-CH₃ H OCH₂CO₂CH₂CCl₃ 3-60 3-CH₃ H OCH₂CO₂CH₂CH═CH₂ 3-61 4-CH₃ HOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 3-62 4-CH₃ H OCH(CH₃)CO₂CH₃ 3-63 4-CH₃ HOCH(CH₃)CO₂CH₂CH₃ 3-64 4-CH₃ H OCH(CH₃)CO₂CH₂CH₂CH₃ 3-65 4-CH₃ IOCH(CH₃)CO₂Cl(CH₃)₂ 3-66 4-CH₃ H OCH(CH₃)CO₂C(CH₃)₃ 3-67 4-CH₃ HOCH(CH₃)CO₂CH₂CH₂F 3-68 4-CH₃ H OCH(CH₃)CO₂CH₂CH₂Cl 3-69 4-CH₃ HOCH(CH₃)CO₂CH₂CCH₃ 3-70 4-CH₃ H OCH(CH₃)CO₂CH₂CH═CH₂ 3-71 4-CH₃ HOCH₂CO₂CH₂CH₂CH₂CH₃ 3-72 4-CH₃ H OCH₂CO₂CH₃ 3-73 4-CH₃ H OCH₂CO₂CH₂CH₃3-74 4-CH₃ H OCH₂CO₂CH₂CH₂CH₃ 3-75 4-CH₃ H OCH₂CO₂CH(CH₃)₂ 3-76 4-CH₃ HOCH₂CO₂C(CH₃)₃ 3-77 4-CH₃ H OCH₂CO₂CH₂CH₂F 3-78 4-CH₃ H OCH₂CO₂CH₂CH₂Cl3-79 4-CH₃ H OCH₂CO₂CH₂CCH₃ 3-80 4-CH₃ H OCH₂CO₂CH₂Cl═CH₂ 3-81 3-OCH₃ HOCH(CH₃)CO₂CH₃ 3-82 3-OCH₃ H OCH(CH₃)CO₂CH₂CH₃ 3-83 3-OCH₃ HOCH(CH₃)CO₂CH₂CH₂CH₃ 3-84 3-OCH₃ H OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 3-85 3-OCH₃ HOCH(CH₃)CO₂CH(CH₃)₂ 3-86 3-OCH₃ H OCH(CH₃)CO₂C(CH₃)₃ 3-87 3-OCH₃ HOCH(CH₃)CO₂CH₂CH₂F 3-88 3-OCH₃ H OCH(CH₃)CO₂CH₂CH₂Cl 3-89 3-OCH₃ HOCH(CH₃)CO₂CH₂CCl₃ 3-90 3-OCH₃ H OCH(CH₃)CO₂CH₂CH═CH₂ 3-91 3-OCH₃ HOCH₂CO₂CH₃ 3-92 3-OCH₃ H OCH₂CO₂CH₂CH₃ 3-93 3-OCH₃ H OCH₂CO₂CH₂CH₂CH₃3-94 3-OCH₃ H OCH₂CO₂CH₂CH₂CH₂CH₃ 3-95 3-OCH₃ H OCH₂CO₂CH(CH₃)₂ 3-963-OCH₃ H OCH₂CO₂C(CH₃)₃ 3-97 3-OCH₃ H OCH₂CO₂CH₂CH₂F 3-98 3-OCH₃ HOCH₂CO₂CH₂CH₂Cl 3-99 3-OCH₃ H OCH₂CO₂CH₂CCl₃ 3-100 3-OCH₃ HOCH₂CO₂CH₂CH═CH₂ 3-101 4-OCH₃ H OCH(CH₃)CO₂CH₃ 3-102 4-OCH₃ HOCH(CH₃)CO₂CH₂CH₃ 3-103 4-OCH₃ H OCH(CH₃)CO₂CH₂CH₂CH₃ 3-104 4-OCH₃ HOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 3-105 4-OCH₃ H OCH(CH₃)CO₂CH(CH₃)₂ 3-106 4-OCH₃H OCH(CH₃)CO₂C(CH₃)₃ 3-107 4-OCH₃ H OCH(CH₃)CO₂CH₂CH₂F 3-108 4-OCH₃ HOCH(CH₃)CO₂CH₂CH₂Cl 3-109 4-OCH₃ H OCH(CH₃)CO₂CH₂CCl₃ 3-110 4-OCH₃ HOCH(CH₃)CO₂CH₂CH═CH₂ 3-111 4-OCH₃ H OCH₂CO₂CH₃ 3-112 4-OCH₃ HOCH₂CO₂CH₂CH₃ 3-113 4-OCH₃ H OCH₂CO₂CH₂CH₂CH₃ 3-114 4-OCH₃ HOCH₂CO₂CH₂CH₂CH₂CH₃ 3-115 4-OCH₃ H OCH₂CO₂CH(CH₃)₂ 3-116 4-OCH₃ HOCH₂CO₂C(CH₃)₃ 3-117 4-OCH₃ H OCH₂CO₂CH₂CH₂F 3-118 4-OCH₃ HOCH₂CO₂CH₂CH₂Cl 3-119 4-OCH₃ H OCH₂CO₂CH₂CCl₃ 3-120 4-OCH₃ HOCH₂CO₂CH₂CH═CH₂ 3-121 3-Cl H OCH(CH₃)CO₂CH₃ 3-122 3-Cl HOCH(CH₃)CO₂CH₂CH₃ 3-123 3-Cl H OCH(CH₃)CO₂CH₂CH₂CH₃ 3-124 3-Cl HOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 3-125 3-Cl H OCH(CH₃)CO₂CH(CH₃)₂ 3-126 3-Cl HOCH(CH₃)CO₂C(CH₃)₃ 3-127 3-Cl H OCH(CH₃)CO₂CH₂CH₂F 3-128 3-Cl HOCH(CH₃)CO₂CH₂CH₂Cl 3-129 3-Cl H OCH(CH₃)CO₂CH₂CCl₃ 3-130 3-Cl HOCH(CH₃)CO₂CH₂CH═CH₂ 3-131 3-Cl H OCH₂CO₂CH₃ 3-132 3-Cl H OCH₂CO₂CH₂CH₃3-133 3-Cl H OCH₂CO₂CH₂CH₂CH₃ 3-134 3-Cl H OCH₂CO₂CH₂CH₂CH₂CH₃ 3-1353-Cl H OCH₂CO₂CH(CH₃)₂ 3-136 3-Cl H OCH₂CO₂C(CH₃)₃ 3-137 3-Cl HOCH₂CO₂CH₂CH₂F 3-138 3-Cl H OCH₂CO₂CH₂CH₂Cl 3-139 3-Cl H OCH₂CO₂CH₂CCl₃3-140 3-Cl H OCH₂CO₂CH₂CH═CH₂ 3-141 4-Cl H OCH(CH₃)CO₂CH₃ 3-142 4-Cl HOCH(CH₃)CO₂CH₂CH₃ 3-143 4-Cl H OCH(CH₃)CO₂CH₂CH₂CH₃ 3-144 4-Cl HOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 3-145 4-Cl H OCH(CH₃)CO₂CH(CH₃)₂ 3-146 4-Cl HOCH(CH₃)CO₂C(CH₃)₃ 3-147 4-Cl H OCH(CH₃)CO₂CH₂CH₂F 3-148 4-Cl HOCH(CH₃)CO₂CH₂CH₂Cl 3-149 4-Cl H OCH(CH₃)CO₂CH₂CCl₃ 3-150 4-Cl HOCH(CH₃)CO₂CH₂CH═CH₂ 3-151 4-Cl H OCH₂CO₂CH₃ 3-152 4-Cl H OCH₂CO₂CH₂CH₃3-153 4-Cl H OCH₂CO₂CH₂CH₂CH₃ 3-154 4-Cl H OCH₂CO₂CH₂CH₂CH₂CH₃ 3-1554-Cl H OCH₂CO₂CH(CH₃)₂ 3-156 4-Cl H OCH₂CO₂C(CH₃)₃ 3-157 4-Cl HOCH₂CO₂CH₂CH₂F 3-158 4-Cl H OCH₂CO₂CH₂CH₂Cl 3-159 4-Cl H OCH₂CO₂CH₂CCl₃3-160 4-Cl H OCH₂CO₂CH₂CH═CH₂ 3-161 H H NHCH(CH₃)CO₂CH₃ 3-162 H HNHCH(CH₃)CO₂CH₂CH₃ 3-163 H H NHCH(CH₃)CO₂CH₂CH₂CH₃ 3-164 H HNHCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 3-165 H H NHCH(CH₃)CO₂CH(CH₃)₂ 3-166 H HNHCH(CH₃)CO₂C(CH₃)₃ 3-167 H H NHCH(CH₃)CO₂CH₂CH₂F 3-168 H HNHCH(CH₃)CO₂CH₂CH₂Cl 3-169 H H NHCH(CH₃)CO₂CH₂CCl₃ 3-170 H HNHCH(CH₃)CO₂CH₂CH═CH₂ 3-171 H H NHCH₂CO₂CH₃ 3-172 H H NHCH₂CO₂CH₂CCl₃3-173 H H NHCH₂CO₂CH₂CH₂CH₃ 3-174 H H NHCH₂CO₂CH₂CH₂CH₂CH₃ 3-175 H HNHCH₂CO₂CH(CH₃)₂ 3-176 H H NHCH₂CO₂C(CH₃)₃ 3-177 H H NHCH₂CO₂CH₂CH₂F3-178 H H NHCH₂CO₂CH₂CH₂Cl 3-179 H H NHCH₂CO₂CH₂CCl₃ 3-180 H HNHCH₂CO₂CH₂CH═CH₂ 3-181 H H N(CH₃)CH(CH₃)CO₂CH₃ 3-182 H HN(CH₃)CH(CH₃)CO₂CH₂CH₃ 3-183 H H N(CH₃)CH₂CO₂CH₃ 3-184 H HN(CH₃)CH₂CO₂CH₂CH₃ 3-185 H H N(CH₃)CH₂CO₂CH₂CH₂CH₃ 3-186 H HOCH(CH₃)CO₂CH₂CH₂CH═CH₂ 3-187 H H OCH(CH₃)CO₂CH₂CH(CH₃)₂ 3-188 H HOCH(CH₃)CO₂CH(CH₃)CH₂CH₃ 3-189 H H OCH(CH₃)CO₂CH₂CH₂CH₂CH₂CH₃ 3-190 H HOCH(CH₃)CO₂CH₂CH₂CH(CH₃)₂ 3-191 H H OCH(CH₃)CO₂CH₂CH(CH₃)CH₂CH₃ 3-192 HH OCH(CH₃)CO₂CH(CH₃)CH₂CH₂CH₃ 3-193 H H OCH(CH₃)CO₂C(CH₃)₂CH₂CH₃ 3-194 HH OCH(CH₃)CO₂CH(CH₃)CH(CH₃)₂ 3-195 H H OCH(CH₃)CO₂CH₂C(CH₃)₃ 3-196 H HOCH(CH₃)CO₂CH₂C═CH 3-197 H H OCH(CH₃)CO₂CH₂CH₂CH═CH₂ 3-198 H HOCH₂CO₂CH₂CH(CH₃)₂ 3-199 H H OCH₂CO₂CH(CH₃)CH₂CH₃ 3-200 H HOCH₂CO₂CH₂CH₂CH₂CH₂CH₃ 3-201 H H OCH₂CO₂CH₂C═CH

[0870] Compound of the formula [I-4] (compound numbers are described inTable 4) TABLE 4

Compound No X¹ X³ X⁴ A 4-1 NO₂ H H OCH(CH₃)CO₂H 4-2 F H H OCH(CH₃)CO₂H4-3 Br H H OCH(CH₃)CO₂H 4-4 CN H H OCH(CH₃)CO₂H 4-5 NO₂ H HOCH(CH₃)CO₂CH₃ 4-6 Br H H OCH(CH₃)CO₂CH₃ 4-7 CN H H OCH(CH₃)CO₂CH₃ 4-8NO₂ H H OCH(CH₃)CO₂CH₂CH₃ 4-9 F 4-CH₃ H OCH(CH₃)CO₂CH₂CH₃ 4-10 CN H HOCH(CH₃)CO₂CH₂CH₃ 4-11 Br H H OCH(CH₃)CO₂CH₂CH₂CH₃ 4-12 CN 4-CH₃ HOCH(CH₃)CO₂CH₂CH₂CH₃ 4-13 NO₂ 5-CH₃ H OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 4-14 CN HH OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 4-15 NO₂ H H OCH₂CO₂H 4-16 F H H OCH₂CO₂H 4-17Br H H OCH₂CO₂H 4-18 CN H H OCH₂CO₂H 4-19 NO₂ H H OCH₂CO₂CH₃ 4-20 F H HOCH₂CO₂CH₃ 4-21 Br H H OCH₂CO₂CH₃ 4-22 CN H H OCH₂CO₂CH₃ 4-23 CN 4-CH₃ HOCH₂CO₂CH₃ 4-24 NO₂ 5-CH₃ H OCH₂CO₂CH₃ 4-25 NO₂ H H OCH₂CO₂CH₂CH₃ 4-26 FH H OCH₂CO₂CH₂CH₃ 4-27 Br H H OCH₂CO₂CH₂CH₃ 4-28 CN H H OCH₂CO₂CH₂CH₃4-29 NO₂ 4-CH₃ H OCH₂CO₂CH₂CH₃ 4-30 CN 4-CH₃ H OCH₂CO₂CH₂CH₃ 4-31 NO₂5-CH₃ H OCH₂CO₂CH₂CH₃ 4-32 CN 5-CH₃ H OCH(CH₃)CO₂CH₃ 4-33 NO₂ H HOCH₂CO₂CH₂CH₂CH₃ 4-34 CN H H OCH₂CO₂CH₂CH₂CH₃ 4-35 NO₂ H HOCH₂CO₂CH₂CH₂CH₂CH₃ 4-36 CN H H OCH₂CO₂CH₂CH₂CH₂CH₃

[0871] Compound of the formula [I-5] (compound numbers are described inTable 5) TABLE 5

Compound No X¹ X³ X⁴ A 5-1 NO₂ H H OCH(CH₃)CO₂H 5-2 F H H OCH(CH₃)CO₂H5-3 Br H H OCH(CH₃)CO₂H 5-4 CN H H OCH(CH₃)CO₂H 5-5 NO₂ H HOCH(CH₃)CO₂CH₃ 5-6 Br H H OCH(CH₃)CO₂CH₃ 5-7 CN H H OCH(CH₃)CO₂CH₃ 5-8NO₂ H H OCH(CH₃)CO₂CH₂CH₃ 5-9 F 4-CH₃ H OCH(CH₃)CO₂CH₂CH₃ 5-10 CN H HOCH(CH₃)CO₂CH₂CH₃ 5-11 Br H H OCH(CH₃)CO₂CH₂CH₂CH₃ 5-12 CN 4-CH₃ HOCH(CH₃)CO₂CH₂CH₂CH₃ 5-13 NO₂ 5-CH₃ H OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 5-14 CN HH OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 5-15 NO₂ H H OCH₂CO₂H 5-16 F H H OCH₂CO₂H 5-17Br H H OCH₂CO₂H 5-18 CN H H OCH₂CO₂H 5-19 NO₂ H H OCH₂CO₂CH₃ 5-20 F H HOCH₂CO₂CH₃ 5-21 Br H H OCH₂CO₂CH₃ 5-22 CN H H OCH₂CO₂CH₃ 5-23 CN 4-CH₃ HOCH₂CO₂CH₃ 5-24 NO₂ 5-CH₃ H OCH₂CO₂CH₃ 5-25 NO₂ H H OCH₂CO₂CH₂CH₃ 5-26 FH H OCH₂CO₂CH₂CH₃ 5-27 Br H H OCH₂CO₂CH₂CH₃ 5-28 CN H H OCH₂CO₂CH₂CH₃5-29 NO₂ 4-CH₃ H OCH₂CO₂CH₂CH₃ 5-30 CN 4-CH₃ H OCH₂CO₂CH₂CH₃ 5-31 NO₂5-CH₃ H OCH₂CO₂CH₂CH₃ 5-32 CN 5-CH₃ H OCH(CH₃)CO₂CH₃ 5-33 NO₂ H HOCH₂CO₂CH₂CH₂CH₃ 5-34 CN H H OCH₂CO₂CH₂CH₂CH₃ 5-35 NO₂ H HOCH₂CO₂CH₂CH₂CH₂CH₃ 5-36 CN H H OCH₂CO₂CH₂CH₂CH₂CH₃

[0872] Next, some of the typical intermediates useful for producing thepresent compound are shown below. The intermediates are specified bycombining the formula described below with sub-number which determinescombination of substituents as shown in Table 6. (For example,intermediate A1-1 is a compound having a general formula [A1-] whereinthe substituents X¹, X² and A are those described in sub-number 1 inTable 6.)

TABLE 6 sub- number X¹ X² A 1 Cl F OCH₃ 2 Cl F OCH₂CH₃ 3 Cl F OCH(CH₃)₂4 Cl F OH 5 Cl F OCH₂Ph 6 Cl F OCH(CH₃)CO₂H 7 Cl F OCH(CH₃)CO₂CH₃ 8 Cl FOCH(CH₃)CO₂CH₂CH₃ 9 Cl F OCH(CH₃)CO₂CH₂CH═CH₂ 10 Cl FOCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 11 Cl F OCH(CH₃)CO₂CH(CH₃)₂ 12 Cl FOCH(CH₃)CO₂CH₂CH(CH₃)₂ 13 Cl F OCH(CH₃)CO₂CH(CH₃)CH₂CH₃ 14 Cl FOCH(CH₃)CO₂CH₂CH₂CH₂CH₂CH₃ 15 Cl F OCH(CH₃)CO₂CH₂CH₂CH(CH₃)₂ 16 Cl FOCH(CH₃)CO₂CH₂CH(CH₃)CH₂CH₃ 17 Cl F OCH(CH₃)CO₂CH(CH₃)CH₂CH₂CH₃ 18 Cl FOCH(CH₃)CO₂CH(CH₃)CH(CH₃)₂ 19 Cl F OCH(CH₃)CO₂CH₂C(CH₃)₃ 20 Cl FOCH(CH₃)CO₂CH₂C≡CH 21 Cl F OCH₂CO₂H 22 Cl F OCH₂CO₂CH₃ 23 Cl FOCH₂CO₂CH₂CH₃ 24 Cl F OCH₂CO₂CH₂CH═CH₂ 25 Cl F OCH₂CO₂CH₂CH₂CH₂CH₃ 26 ClF OCH(CH₃)CO₂CH(CH₃)₂ 27 Cl F OCH(CH₃)CO₂CH₂CH(CH₃)₂ 28 Cl FOCH(CH₃)CO₂CH(CH₃)CH₂CH₃ 29 Cl F OCH(CH₃)CO₂CH₂CH₂CH₂CH₂CH₃ 30 Cl FOCH(CH₃)CO₂CH₂CH₂CH(CH₃)₂ 31 Cl F OCH(CH₃)CO₂CH₂CH(CH₃)CH₂CH₃ 32 Cl FOCH(CH₃)CO₂CH(CH₃)CH₂CH₂CH₃ 33 Cl F OCH(CH₃)CO₂CH(CH₃)CH(CH₃)₂ 34 Cl FOCH(CH₃)CO₂CH₂C(CH₃)₃ 35 Cl F OCH(CH₃)CO₂CH₂C≡CH 36 Br F OCH₃ 37 Br FOCH₂CH₃ 38 Br F OCH(CH₃)₂ 39 Br F OH 40 Br F OCH₂Ph 41 Br F OCH(CH₃)CO₂H42 Br F OCH(CH₃)CO₂CH₃ 43 Br F OCH(CH₃)CO₂CH₂CH₃ 44 Br FOCH(CH₃)CO₂CH₂CH═CH₂ 45 Br F OCH(CH₃)CO₂CH₂CH₂CH₂CH₃ 46 Br FOCH(CH₃)CO₂CH(CH₃)₂ 47 Br F OCH(CH₃)CO₂CH₂CH(CH₃)₂ 48 Br FOCH(CH₃)CO₂CH(CH₃)CH₂CH₃ 49 Br F OCH(CH₃)CO₂CH₂CH₂CH₂CH₂CH₃ 50 Br FOCH(CH₃)CO₂CH₂CH₂CH(CH₃)₂ 51 Br F OCH(CH₃)CO₂CH₂CH(CH₃)CH₂CH₃ 52 Br FOCH(CH₃)CO₂CH(CH₃)CH₂CH₂CH₃ 53 Br F OCH(CH₃)CO₂CH(CH₃)CH(CH₃)₂ 54 Br FOCH(CH₃)CO₂CH₂C(CH₃)₃ 55 Br F OCH(CH₃)CO₂CH₂C≡CH 56 Br F OCH₂CO₂H 57 BrF OCH₂CO₂CH₃ 58 Br F OCH₂CO₂CH₂CH₃ 59 Br F OCH₂CO₂CH₂CH═CH₂ 60 Br FOCH₂CO₂CH₂CH₂CH₂CH₃ 61 Br F OCH(CH₃)CO₂CH(CH₃)₂ 62 Br FOCH(CH₃)CO₂CH₂CH(CH₃)₂ 63 Br F OCH(CH₃)CO₂CH(CH₃)CH₂CH₃ 64 Br FOCH(CH₃)CO₂CH₂CH₂CH₂CH₂CH₃ 65 Br F OCH(CH₃)CO₂CH₂CH₂CH(CH₃)₂ 66 Br FOCH(CH₃)CO₂CH₂CH(CH₃)CH₂CH₃ 67 Br F OCH(CH₃)CO₂CH(CH₃)CH₂CH₂CH₃ 68 Br FOCH(CH₃)CO₂CH(CH₃)CH(CH₃)₂ 69 Br F OCH(CH₃)CO₂CH₂C(CH₃)₃ 70 Br FOCH(CH₃)CO₂CH₂C≡CH 71 NO₂ F OCH₃ 72 NO₂ F OCH₂CH₃ 73 NO₂ F OCH(CH₃)₂ 74NO₂ F OH 75 NO₂ F OCH₂Ph 76 NO₂ F OCH(CH₃)CO₂H 77 NO₂ F OCH(CH₃)CO₂CH₃78 NO₂ F OCH(CH₃)CO₂CH₂CH₃ 79 NO₂ F OCH(CH₃)CO₂CH₂CH═CH₂ 80 NO₂ FOCH₂CO₂H 81 NO₂ F OCH₂CO₂CH₃ 82 NO₂ F OCH₂CO₂CH₂CH₃ 83 NO₂ FOCH₂CO₂CH₂CH═CH₂ 84 CN F OCH₃ 85 CN F OCH₂CH₃ 86 CN F OCH(CH₃)₂ 87 CN FOH 88 CN F OCH₂Ph 89 CN F OCH(CH₃)CO₂H 90 CN F OCH(CH₃)CO₂CH₃ 91 CN FOCH(CH₃)CO₂CH₂CH₃ 92 CN F OCH(CH₃)CO₂CH₂CH═CH₂ 93 CN F OCH₂CO₂H 94 CN FOCH₂CO₂CH₃ 95 CN F OCH₂CO₂CH₂CH₃ 96 CN F OCH₂CO₂CH₂CH═CH₂

[0873] Next, the formulation examples of the present compounds areexplained. In the examples, the present compounds are shown as CompoundNo. in Tables 1 to 5, and “part(s)” shows “part(s) by weight”.

FORMULATION EXAMPLE 1

[0874] Fifty (50) parts of each of the present compounds 1-1 to 1-201,2-1 to 2-201, 3-1 to 3-201, 4-1 to 4-36 and 5-1 to 5-36, 3 parts ofcalcium ligninsulfonate, 2 parts of sodium laurylsulfate, and 45 partsof synthetic hydrated silicon dioxide are well pulverized and mixed, toobtain each of the wettable powders.

FORMULATION EXAMPLE 2

[0875] Ten (10) parts of each of the present compound 1-1 to 1-201, 2-1to 2-201, 3-1 to 3-201, 4-1 to 4-36 and 5-1 to 5-36, 14 parts ofpolyoxyethylenestyryl phenyl ether, 6 parts of calciumdodecylbenzenesulfonate, 35 parts of xylene, and 35 parts ofcyclohexanone are mixed to obtain each of the emulsifiable concentrates.

FORMULATION EXAMPLE 3

[0876] Two (2) parts of each of the present compound 1-1 to 1-201, 2-1to 2-201, 3-1 to 3-201, 4-1 to 4-36 and 5-1 to 5-36, 2 parts ofsynthetic hydrated silica, 2 parts of calcium ligninsulfonate, 30 partsof bentonite, and 64 parts of kaolin clay are well pulverized and mixed,and after adding water and well kneading, that is granulated and driedto obtain each of the granules.

FORMULATION EXAMPLE 4

[0877] Twenty-five (25) parts of each of the present compound 1-1 to1-201, 2-1 to 2-201, 3-1 to 3-201, 4-1 to 4-36 and 5-1 to 5-36, 50 partsof a 10% aqueous solution of polyvinyl alcohol, and 25 parts of waterare mixed, are wet pulverized until the average particle diameter is 5μm or less, to obtain each of the flowables.

FORMULATION EXAMPLE 5

[0878] Five(5) parts of each of the present compound 1-1 to 1-201, 2-1to 2-201, 3-1 to 3-201, 4-1 to 4-36 and 5-1 to 5-36 is added into 40parts of 10% aqueous solution of polyvinyl alcohol, and the mixture isemulsified and dispersed until the average diameter is 10 μm or less byhomogenizer. Next, 55 parts of water is added to the resultant mixtureto obtain each of the concentrated emulsion.

[0879] Next, test examples are explained to show that the presentcompounds are effective as an active ingredient of a herbicide. In theexamples, each of the present compounds are shown as Compound No. inTables 1 to 5.

TEST EXAMPLE 1

[0880] A cylindrical plastic pot having a diameter of 10 cm and a depthof 10 cm was filled with soil and then seeded with Ivyleaf morningglory(Ipomoea hederacea), velvetleaf (Abutilon theophrasti), barnyardgrass(Echinochloa crus-galli) and blackgrass (Alopecurus myosuroides). Thesetest plants were grown in a greenhouse for 9 days. Then, each ofcompounds 1-1,2-1, 3-1,3-2, 3-11 and 3-12 was formulated into anemulsifiable concentrate according to Formulation Example 2 and thendiluted to the prescribed amount with water containing a spreading agentand the dilution was uniformly sprayed over the foliage of the testplants with a sprayer at a rate of 1000 liters per hectare After theapplication, the test plants were grown in the greenhouse for 7 days,and the herbicidal activity of the applied composition was determined.As a result, it was determined that the growth of Ivyleaf morningglory,velvetleaf, barnyardgrass and blackgrass was completely controlled whencompounds 1-1,2-1, 3-1,3-2, 3-11 and 3-12 were applied at the dosage of125 g/ha, respectively.

TEST EXAMPLE 2

[0881] A cylindrical plastic pot having a diameter of 10 cm and a depthof 10 cm was filled with soil and then seeded with Ivyleaf morningglory(Ipomoea hederacea), velvetleaf (Abutilon theophrasti) and barnyardgrass(Echinochloa crus-galli). Then, each of the compounds 1-1,2-1 and 3-1was formulated into an emulsifiable concentrate according to FormulationExample 2 and then diluted to the prescribed amount with water, and thedilution was uniformly sprayed over the surface of the soil with asprayer at a rate of 1000 liters per hectare. After the application, thetest plants were grown in the greenhouse for 7 days, and the herbicidalactivity of the applied composition was examined. The emergence ofivyleaf morningglory, velvetleaf and barnyardgrass were completelycontrolled when compounds 1-1,2-1 and 3-1 were applied at the dosage of500 g/ha, respectively.

TEST EXAMPLE 3

[0882] A cylindrical plastic pot having a diameter of 10 cm and a depthof 10 cm was filled with soil and then seeded with Ivyleaf morningglory(Ipomoea hederacea), velvetleaf (Abutilon theophrasti) and barnyardgrass(Echinochloa crus-galli). These test plants were grown in a greenhousefor 9 days. After then, each of the compounds 3-16, 3-20 and 3-198 wasformulated into an emulsifiable concentrate according to FormulationExample 2 and then diluted to the prescribed amount with watercontaining a spreading agent and the dilution was uniformly sprayed overthe foliage of the test plants with a sprayer at a rate of 1000 litersper hectare. After the application, the test plants were grown in thegreenhouse for 7 days, and the herbicidal activity was examined. As aresult, it was determined that the growth of Ivyleaf morningglory,velvetleaf and barnyardgrass was completely controlled when compounds3-16, 3-20 and 3-198 were applied at the dosage of 500 g/ha,respectively.

TEST EXAMPLE 4

[0883] A cylindrical plastic pot having a diameter of 10 cm and a depthof 10 cm was filled with soil and then seeded with Ivyleaf morningglory(Ipomoea hederacea), velvetleaf (Abutilon theophrasti), barnyardgrass(Echinochloa crus-galli) and blackgrass (Alopecurus myosuroides). Then,each of the compounds 3-2,3-11, 3-12, 3-16, 3-20 and 3-198 wasformulated into an emulsifiable concentrate according to FormulationExample 2 and then diluted to the prescribed amount with water, and thedilution was uniformly sprayed over the surface of the soil with asprayer at a rate of 1000 liters per hectare. After the application, thetest plants were grown in the greenhouse for 7 days, and the herbicidalactivity of the applied composition was examined. The emergence ofIvyleaf morningglory, velvetleaf, barnyardgrass and blackgrass werecompletely controlled when compounds 3-2, 3-11, 3-12, 3-16, 3-20 and3-198 were applied at the dosage of 2000 g/ha, respectively.

[0884] In the following test examples, the herbicidal activity wasevaluated at 11 levels with indices of 0 to 10, i.e., designated by thenumeral “0”, “1”, “2”, “3”, “4”, “5”, “6”, “7”, “8”, “9” or “10” wherein“0” means that there was no or little difference in the degree ofgermination or growth between the treated and the untreated testedplants at the time of examination, and “10” means that the test plantsdied complete or their germination or growth was completely inhibited.TABLE 7 Com- pound No Structure Note A

WO 98/41093 B

WO 97/01541 C

WO 97/01541

TEST EXAMPLE 5

[0885] A cylindrical plastic pot having a diameter of 18.5 cm and adepth of 15 cm was filled with soil and then seeded with commonchickweed (Stellaria media). These test plants were grown in agreenhouse for 29 days. After then, each of the compound 1-2 andCompound A was formulated into an emulsifiable concentrate according toFormulation Example 2 and then diluted to the prescribed amount withwater containing a spreading agent and the dilution was uniformlysprayed over the foliage of the test plants with a sprayer at a rate of1000 liters per hectare. After the application, the test plants weregrown in the greenhouse for 9 days, and the herbicidal activity wasexamined. The results are shown in the following Table 8. TABLE 8 DosageCompound No (g/ha) Herbicidal activity 1-2 10 10 A 10  5

TEST EXAMPLE 6

[0886] A plastic pot (27 cm×19 cm×7 cm) was filled with soil and thenseeded with Johnsongrass (Sorghum halepense), Giant foxtail (Setariafaberi), barnyardgrass (Echinochloa crus-galli), large crabgrass(Digitaria sanguinalis), Broadleaf signalgrass (Brachiaria platyphylla)and wild oat (Avena fatua). These test plants were grown in a greenhousefor 25 days. After then, each of the compounds 3-11, 4-22, B and C wasformulated into an emulsifiable concentrate according to FormulationExample 2 and then diluted to the prescribed amount with watercontaining a spreading agent and the dilution was uniformly sprayed overthe foliage of the test plants with a sprayer at a rate of 1000 litersper hectare. After the application, the test plants were grown in thegreenhouse for 4 days, and the herbicidal activity was examined. Theresults are shown in the following Table 9. (In the Table 9, the testplants are shown as follows. Johnsongrass: J , Giant foxtail: GF,Barnyardgrass: B Large crabgrass: LC, Broadleaf signalgrass: BC wildoat: W TABLE 9 Compound Doasage Herbicidal activity No. (g/ha) J GF B LCBC W 3-11 3.3 10 9 10 10 10 10 1 9 9 8 9 9 10 0.33 8 8 7 8 8 8 4-22 3.39 10 9 9 9 10 1 8 8 9 9 8 9 0.33 8 7 8 9 8 8 B 3.3 7 7 7 8 8 7 1 7 5 6 76 5 0.33 2 3 2 3 2 2 C 3.3 6 4 6 5 6 5 1 4 3 4 3 3 3 0.33 2 1 1 2 2 1

What is claimed is:
 1. An uracil compound of the formula [I]:

wherein W represents oxygen, sulfur, imino or C₁ to C₃ alkylimino; Yrepresents oxygen, sulfur, imino or C₁ to C₃ alkylimino; R¹ representsC₁ to C₃ alkyl or C₁ to C₃ haloalkyl; R²represents C₁ to C₃ alkyl; R⁴represents hydrogen or methyl; R⁵ represents C₁to C₆alkyl, C₁ to C₆haloalkyl, C₃ to C₆ alkenyl, C₃ to C₆ haloalkenyl, C₃ to C₆ alkynyl orC₃ to C₆ haloalkynyl; X¹ represents halogen, cyano or nitro; X²represents hydrogen or halogen; and each of X³ and X⁴ independentlyrepresents hydrogen, halogen, C₁ to C₆ alkyl, C₁ to C₆ haloalkyl, C₃ toC₆ alkenyl, C₃ to C₆ haloalkenyl, C₃ to C₆ alkynyl, C₃ to C₆haloalkynyl, C₁ to C₆ alkoxy C₁ to C₆ alkyl, C₃ to C₆ alkoxy, C₁ to C₆haloalkoxy, C₁ to C₆ alkoxycarbonyl C₁ to C₆ alkoxy or cyano.
 2. Theuracil compound according to claim 1, wherein
 3. The uracil compoundaccording to claim 1, wherein X¹ is chlorine.
 4. The uracil compoundaccording to claim 1, wherein X² is fluorine.
 5. The uracil compoundaccording to claim 1 or 2, wherein the substitution position of W isortho-position of Y on the benezene ring.
 6. The uracil compoundaccording to claim 1 or 2, wherein W is oxygen.
 7. The uracil compoundaccording to claim 1 or 2, wherein R¹ is methyl or trifluoromethyl. 8.The uracil compound according to claim 1 or 2, wherein R² is methyl. 9.The uracil compound according to claim 1 or 2, wherein X³ and X⁴ arehydrogen.
 10. The uracil compound according to claim 1 or 2, wherein R⁵is methyl or ethyl.
 11. A herbicidal composition which comprises theuracil compound according to claim 1, and inert carrier or diluent. 12.A method for controlling weeds, which comprises applying an effectiveamount of the uracil compound according to claim 1 to weeds or a placewhere the weeds grow or will grow.
 13. An uracil compound of the formula[VII]:

wherein W represents oxygen, sulfur, imino or C₁ to C₃ alkylimino; Yrepresents oxygen, sulfur atom, imino or C₁ to C₃ alkylimino; R¹represents C₁ to C₃ alkyl or C₁ to C₃ haloalkyl; R² represents C₁ to C₃alkyl; R⁴ represents hydrogen or methyl; X¹ represents halogen, cyano ornitro; X² represents hydrogen or halogen, and each of X³ and X⁴independently represents hydrogen, halogen, C₁ to C₆ alkyl, C₁ to C₆haloalkyl, C₃ to C₆ alkenyl, C₃ to C₆ haloalkenyl, C₃ to C₆ alkynyl, C₃to C₆ haloalkynyl, C₁ to C₆ alkoxy C₁ to C₆ alkyl, C₁ to C₆ alkoxy, C₁to C₆ haloalkoxy, C₁ to C₆ alkoxycarbonyl C₁ to C₆ alkoxy or cyano. 14.The uracil compound according to claim 13, wherein the substitutionposition of W is ortho-position of Y on the benzene ring.
 15. An anilinecompound of the formula [XXXII]:

wherein W represents oxygen, sulfur, imino or C₁ to C₃ alkylimino; R¹⁷represents oxygen or sulfur; R⁴ represents hydrogen or methyl; R⁵represents C₁ to C₆ alkyl, C₁ to C₆ haloalkyl, C₃ to C₆ alkenyl, C₃ toC₆ haloalkenyl, C₃ to C₆ alkynyl, C₃ to C₆ haloalkynyl; X¹ representshalogen, cyano, nitro; X² represents hydrogen or halogen, and each of X³and X⁴independently represents hydrogen, halogen, C₁ to C₆ alkyl, C₁ toC₆ haloalkyl, C₃ to C₆ alkenyl, C₃ to C₆ haloalkenyl, C₃ to C₆ alkynyl,C₃ to C₆ haloalkynyl, C₁ to C₆ alkoxy C₁ to C₆ alkyl, C₁ to C₆ alkoxy,C₁ to C₆ haloalkoxy, C₁ to C₆ alkoxycarbonyl C₁ to C₆ alkoxy or cyano.16. The uracil compound according to claim 15, wherein the substitutionposition of W is ortho-position of R¹⁷ on the benzene ring.
 17. Methyl[2-(5-amino-2-chloro-4-fluorophenoxy) phenoxy]acetate.
 18. Ethyl[2-(5-amino-2-chloro-4-fluorophenoxy) phenoxy]acetate.
 19. A compound ofthe formula [XXXIV]:

wherein W represents oxygen, sulfur, imino or C₁ to C₃ alkylimino; R¹⁷represents oxygen or sulfur; R⁴ represents hydrogen or methyl; R⁵represents C₁ to C₆ alkyl, C₁ to C₆ haloalkyl, C₃ to C₆ alkenyl, C₃ toC₆ haloalkenyl, C₃ to C₆ alkynyl, C₃ to C₆ haloalkynyl; R¹⁸ representsC₁ to C₆ alkyl or phenyl; X¹ represents halogen, cyano, nitro; X²represents hydrogen or halogen; and each of X³ and X⁴ independentlyrepresents hydrogen, halogen, C₁ to C₆ alkyl, C₁ to C₆ haloalkyl, C₃ toC₆ alkenyl, C₃ to C₆ haloalkenyl, C₃ to C₆ alkynyl, C₃ to C₆haloalkynyl, C₁ to C₆ alkoxy C₁ to C₆ alkyl, C₁ to C₆ alkoxy, C₁ to C₆haloalkoxy, C₁ to C₆ alkoxycarbonyl C₁ to C₆ alkoxy or cyano.
 20. Theuracil compound according to claim 19, wherein the substitution positionof W is ortho-position of R¹⁷ on the benzene ring.
 21. A compound of theformula [XXXIII]:

wherein W represents oxygen, sulfur, imino or C₁ to C₃ alkylimino; R¹⁷represents oxygen or sulfur; R⁴ represents hydrogen or methyl; R⁵represents C₁ to C₆ alkyl, C₁ to C₆ haloalkyl, C₃ to C₆ alkenyl, C₃ toC₆ haloalkenyl, C₃ to C₆ alkynyl, C₃ to C₆ haloalkynyl; X¹ representshalogen, cyano or nitro; X² represents hydrogen or halogen; and each ofX³ and X⁴ independently represents hydrogen, halogen, C₁ to C₆ alkyl, C₁to C₆ haloalkyl, C₃ to C₆ alkenyl, C₃ to C₆ haloalkenyl, C₃ to C₆alkynyl, C₃ to C₆ haloalkynyl, C₁ to C₆ alkoxy C₁ to C₆ alkyl, C₁ to C₆alkoxy, C₁ to C₆ haloalkoxy, C₁ to C₆ alkoxycarbonyl C₁ to C₆ alkoxy orcyano.
 22. The uracil compound according to claim 21, wherein thesubstitution position of W is ortho-position of R¹⁷ on the benzene ring.23. The uracil compound according to claim 1, wherein R¹ istrifluoromthyl, R² is methyl, R⁴ is hydrogen, R⁵ is methyl, X¹ ischlorine, X² is fluorine, X³ is hydrogen, X⁴ is hydrogen, W is oxygen, Yis oxygen, and the substitution position of W on the benzene ring isortho position of Y.
 24. The uracil compound according to claim 1,wherein R¹ is trifluoromethyl, R² is methyl, R⁴ is hydrogen, R⁵ isethyl, X¹ is chlorine, X² is fluorine, X³ is hydrogen, X⁴ is hydrogen, Wis oxygen, Y is oxygen, and the substitution position of W on thebenzene ring is ortho position of Y.
 25. The uracil compound accordingto claim 3, wherein X² is fluorine.
 26. The uracil compound according toclaim 25, wherein R¹ is trifluoromethyl and R² is methyl.
 27. The uracilcompound according to claim 26, wherein W is oxygen and Y is oxygen orsulfur.
 28. The uracil compound according to claim 27, wherein Y isoxygen.
 29. The uracil compound according to any one of claims 3, 25,27, or 28, wherein the substitution position of W is ortho-position of Yon the benzene ring.
 30. The uracil compound according to claim 28,wherein the substitution position of W is ortho-position of Y on thebenzene ring.
 31. The uracil compound according to claim 13, wherein R¹is trifluoromethyl, R² is methyl, R⁴ is hydrogen or methyl, X¹ ischlorine, X² is fluorine, X³ is hydrogen, X⁴ is hydrogen, W is oxygen, Yis oxygen, and the substitution position of W on the benzene ring isortho-position of Y.
 32. A herbicidal composition which comprises theuracil compound according to any one of claims 23, 24, 25, or 30, andinert carrier or diluent.
 33. A method for controlling weeds, whichcomprises applying an effective amount of the uracil compound accordingto any one of claims 23, 24, 25, or 30 to weeds or a place where theweeds grow or will grow.